Author Archives: admin

Cell therapy – Wikipedia

By adminOctober 21, 2016Uncategorized

Cell therapy (also called cellular therapy or cytotherapy) is therapy in which cellular material is injected into a patient;[1] this generally means intact, living cells. For example, T cells capable of fighting cancer cells via cell-mediated immunity may be injected in the course of immunotherapy.

Cell therapy originated in the nineteenth century when scientists experimented by injecting animal material in an attempt to prevent and treat illness.[2] Although such attempts produced no positive benefit, further research found in the mid twentieth century that human cells could be used to help prevent the human body rejecting transplanted organs, leading in time to successful bone marrow transplantation.[3]

Today two distinct categories of cell therapy are recognized.[1]

The first category is cell therapy in mainstream medicine. This is the subject of intense research and the basis of potential therapeutic benefit.[4] Such research can be controversial when it involves human embryonic material.

The second category is in alternative medicine, and perpetuates the practice of injecting animal materials in an attempt to cure disease. This practice, according to the American Cancer Society, is not backed by any medical evidence of effectiveness, and can have deadly consequences.[1]

Cell therapy can be defined as therapy in which cellular material is injected into a patient.[1]

There are two branches of cell therapy: one is legitimate and established, whereby human cells are transplanted from a donor to a patient; the other is dangerous alternative medicine, whereby injected animal cells are used to attempt to treat illness.[1]

The origins of cell therapy can perhaps be traced to the nineteenth century, when Charles-douard Brown-Squard (18171894) injected animal testicle extracts in an attempt to stop the effects of aging.[2] In 1931 Paul Niehans (18821971) who has been called the inventor of cell therapy attempted to cure a patient by injecting material from calf embryos.[1] Niehans claimed to have treated many people for cancer using this technique, though his claims have never been validated by research.[1]

In 1953 researchers found that laboratory animals could be helped not to reject organ transplants by pre-inoculating them with cells from donor animals; in 1968, in Minnesota, the first successful human bone marrow transplantation took place.[3]

Bone marrow transplants have been found to be effective, along with some other kinds of human cell therapy for example in treating damaged knee cartilage.[1] In recent times, cell therapy using human material has been recognized as an important field in the treatment of human disease.[4] The experimental field of Stem cell therapy has shown promise for new types of treatment.[1]

In mainstream medicine, cell therapy is supported by a distinct healthcare industry which sees strong prospects for future growth.[5][6]

In allogeneic cell therapy the donor is a different person to the recipient of the cells.[7] In pharmaceutical manufacturing, the allogenic methodology is promising because unmatched allogenic therapies can form the basis of "off the shelf" products.[8] There is research interest in attempting to develop such products to treat conditions including Crohn's disease[9] and a variety of vascular conditions.[10]

Research into human embryonic stem cells is controversial, and regulation varies from country to country, with some countries banning it outright. Nevertheless, these cells are being investigated as the basis for a number of therapeutic applications, including possible treatments for diabetes[11] and Parkinson's disease.[12]

Cell therapy is targeted at many clinical indications in multiple organs and by several modes of cell delivery. Accordingly, the specific mechanisms of action involved in the therapies are wide ranging. However, there are two main principles by which cells facilitate therapeutic action:

Neural stem cells (NSCs) are the subject of ongoing research for possible therapeutic applications, for example for treating a number of neurological disorders such as Parkinson's disease and Huntington's disease.[20]

MSCs are immunomodulatory, multipotent and fast proliferating and these unique capabilities mean they can be used for a wide range of treatments including immune-modulatory therapy, bone and cartilage regeneration, myocardium regeneration and the treatment of Hurler syndrome, a skeletal and neurological disorder.[21]

Researchers have demonstrated the use of MSCs for the treatment of osteogenesis imperfecta (OI). Horwitz et al. transplanted bone marrow (BM) cells from human leukocyte antigen (HLA)-identical siblings to patients suffering from OI. Results show that MSCs can develop into normal osteoblasts, leading to fast bone development and reduced fracture frequencies.[22] A more recent clinical trial showed that allogeneic fetal MSCs transplanted in utero in patients with severe OI can engraft and differentiate into bone in a human fetus.[23]

Besides bone and cartilage regeneration, cardiomyocyte regeneration with autologous BM MSCs has also been reported recently. Introduction of BM MSCs following myocardial infarction (MI) resulted in significant reduction of damaged regions and improvement in heart function. Clinical trials for treatment of acute MI with Prochymal by Osiris Therapeutics are underway. Also, a clinical trial revealed huge improvements in nerve conduction velocities in Hurlers Syndrome patients infused with BM MSCs from HLA-identical siblings.[24]

HSCs possess the ability to self-renew and differentiate into all types of blood cells, especially those involved in the human immune system. Thus, they can be used to treat blood and immune disorders. Since human bone marrow (BM) grafting was first published in 1957,[25] there have been significant advancements in HSCs therapy. Following that, syngeneic marrow infusion[26] and allogeneic marrow grafting[27] were performed successfully. HSCs therapy can also render its cure by reconstituting damaged blood-forming cells and restoring the immune system after high-dose chemotherapy to eliminate disease.[28]

There are three types of HSCT: syngeneic, autologous, and allogeneic transplants.[21] Syngeneic transplantations occur between identical twins. Autologous transplantations use the HSCs obtained directly from the patient and hence do not cause any complications of tissue incompatibility; whereas allogeneic transplantations involve the use of donor HSCs, either genetically related or unrelated to the recipient. To lower the risks of transplant, which include graft rejection and Graft-Versus-Host Disease (GVHD), allogeneic HSCT must satisfy compatibility at the HLA loci (i.e. genetic matching to reduce the immunogenicity of the transplant). Mismatch of HLA loci would result in treatment-related mortality and higher risk of acute GVHD.[29]

In addition to BM derived HSCs, the use of alternative sources such as umbilical cord blood (UCB) and peripheral blood stem cells (PBSCs) has been increasing. In comparison with BM derived HSCs recipients, PBSCs recipients afflicted with myeloid malignancies reported a faster engraftment and better overall survival.[30] However, this was at the expense of increased rate of GVHD.[31] Also, the use of UCB requires less stringent HLA loci matching, although the time of engraftment is longer and graft failure rate is higher.[32][33]

In alternative medicine, cell therapy is defined as the injection of non-human cellular animal material in an attempt to treat illness.[1]Quackwatch labels this as "senseless", since "cells from the organs of one species cannot replace the cells from the organs of other species" and because a number of serious adverse effects have been reported.[34]

Of this alternative, animal-based form of cell therapy, the American Cancer Society say: "Available scientific evidence does not support claims that cell therapy is effective in treating cancer or any other disease. In may in fact be lethal ...".[1]

Continue reading here:
Cell therapy - Wikipedia

Cancer – Wikipedia

By adminOctober 21, 2016Stem Cell Treatment

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body.[1][2] Not all tumors are cancerous; benign tumors do not spread to other parts of the body.[2] Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss and a change in bowel movements.[3] While these symptoms may indicate cancer, they may have other causes.[3] Over 100 cancers affect humans.[2]

Tobacco use is the cause of about 22% of cancer deaths.[1] Another 10% is due to obesity, poor diet, lack of physical activity and drinking alcohol.[1][4] Other factors include certain infections, exposure to ionizing radiation and environmental pollutants.[5] In the developing world nearly 20% of cancers are due to infections such as hepatitis B, hepatitis C and human papillomavirus (HPV).[1] These factors act, at least partly, by changing the genes of a cell.[6] Typically many genetic changes are required before cancer develops.[6] Approximately 510% of cancers are due to inherited genetic defects from a person's parents.[7] Cancer can be detected by certain signs and symptoms or screening tests.[1] It is then typically further investigated by medical imaging and confirmed by biopsy.[8]

Many cancers can be prevented by not smoking, maintaining a healthy weight, not drinking too much alcohol, eating plenty of vegetables, fruits and whole grains, vaccination against certain infectious diseases, not eating too much processed and red meat, and avoiding too much sunlight exposure.[9][10] Early detection through screening is useful for cervical and colorectal cancer.[11] The benefits of screening in breast cancer are controversial.[11][12] Cancer is often treated with some combination of radiation therapy, surgery, chemotherapy, and targeted therapy.[1][13] Pain and symptom management are an important part of care. Palliative care is particularly important in people with advanced disease.[1] The chance of survival depends on the type of cancer and extent of disease at the start of treatment.[6] In children under 15 at diagnosis the five-year survival rate in the developed world is on average 80%.[14] For cancer in the United States the average five-year survival rate is 66%.[15]

In 2012 about 14.1 million new cases of cancer occurred globally (not including skin cancer other than melanoma).[6] It caused about 8.2 million deaths or 14.6% of human deaths.[6][16] The most common types of cancer in males are lung cancer, prostate cancer, colorectal cancer and stomach cancer. In females, the most common types are breast cancer, colorectal cancer, lung cancer and cervical cancer.[6] If skin cancer other than melanoma were included in total new cancers each year it would account for around 40% of cases.[17][18] In children, acute lymphoblastic leukaemia and brain tumors are most common except in Africa where non-Hodgkin lymphoma occurs more often.[14] In 2012, about 165,000 children under 15 years of age were diagnosed with cancer. The risk of cancer increases significantly with age and many cancers occur more commonly in developed countries.[6] Rates are increasing as more people live to an old age and as lifestyle changes occur in the developing world.[19] The financial costs of cancer were estimated at $1.16 trillion US dollars per year as of 2010.[20]

Cancers are a large family of diseases that involve abnormal cell growth with the potential to invade or spread to other parts of the body.[1][2] They form a subset of neoplasms. A neoplasm or tumor is a group of cells that have undergone unregulated growth and will often form a mass or lump, but may be distributed diffusely.[21][22]

All tumor cells show the six hallmarks of cancer. These characteristics are required to produce a malignant tumor. They include:[23]

The progression from normal cells to cells that can form a detectable mass to outright cancer involves multiple steps known as malignant progression.[24][25]

When cancer begins, it produces no symptoms. Signs and symptoms appear as the mass grows or ulcerates. The findings that result depend on the cancer's type and location. Few symptoms are specific. Many frequently occur in individuals who have other conditions. Cancer is a "great imitator". Thus, it is common for people diagnosed with cancer to have been treated for other diseases, which were hypothesized to be causing their symptoms.[26]

Local symptoms may occur due to the mass of the tumor or its ulceration. For example, mass effects from lung cancer can block the bronchus resulting in cough or pneumonia; esophageal cancer can cause narrowing of the esophagus, making it difficult or painful to swallow; and colorectal cancer may lead to narrowing or blockages in the bowel, affecting bowel habits. Masses in breasts or testicles may produce observable lumps. Ulceration can cause bleeding that, if it occurs in the lung, will lead to coughing up blood, in the bowels to anemia or rectal bleeding, in the bladder to blood in the urine and in the uterus to vaginal bleeding. Although localized pain may occur in advanced cancer, the initial swelling is usually painless. Some cancers can cause a buildup of fluid within the chest or abdomen.[26]

General symptoms occur due to effects that are not related to direct or metastatic spread. These may include: unintentional weight loss, fever, excessive fatigue and changes to the skin.[27]Hodgkin disease, leukemias and cancers of the liver or kidney can cause a persistent fever.[26]

Some cancers may cause specific groups of systemic symptoms, termed paraneoplastic phenomena. Examples include the appearance of myasthenia gravis in thymoma and clubbing in lung cancer.[26]

Cancer can spread from its original site by local spread, lymphatic spread to regional lymph nodes or by haematogenous spread via the blood to distant sites, known as metastasis. When cancer spreads by a haematogenous route, it usually spreads all over the body. However, cancer 'seeds' grow in certain selected site only ('soil') as hypothesized in the soil and seed hypothesis of cancer metastasis. The symptoms of metastatic cancers depend on the tumor location and can include enlarged lymph nodes (which can be felt or sometimes seen under the skin and are typically hard), enlarged liver or enlarged spleen, which can be felt in the abdomen, pain or fracture of affected bones and neurological symptoms.[26]

The majority of cancers, some 9095% of cases, are due to environmental factors. The remaining 510% are due to inherited genetics.[5]Environmental, as used by cancer researchers, means any cause that is not inherited genetically, such as lifestyle, economic and behavioral factors and not merely pollution.[28] Common environmental factors that contribute to cancer death include tobacco (2530%), diet and obesity (3035%), infections (1520%), radiation (both ionizing and non-ionizing, up to 10%), stress, lack of physical activity and environmental pollutants.[5]

It is not generally possible to prove what caused a particular cancer, because the various causes do not have specific fingerprints. For example, if a person who uses tobacco heavily develops lung cancer, then it was probably caused by the tobacco use, but since everyone has a small chance of developing lung cancer as a result of air pollution or radiation, the cancer may have developed for one of those reasons. Excepting the rare transmissions that occur with pregnancies and occasional organ donors, cancer is generally not a transmissible disease.[29]

Exposure to particular substances have been linked to specific types of cancer. These substances are called carcinogens.

Tobacco smoke, for example, causes 90% of lung cancer.[30] It also causes cancer in the larynx, head, neck, stomach, bladder, kidney, esophagus and pancreas.[31] Tobacco smoke contains over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons.[32]

Tobacco is responsible about one in five cancer deaths worldwide[32] and about one in three in the developed world[33]Lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking rates since the 1950s followed by decreases in lung cancer death rates in men since 1990.[34][35]

In Western Europe, 10% of cancers in males and 3% of cancers in females are attributed to alcohol exposure, especially liver and digestive tract cancers.[36] Cancer from work-related substance exposures may cause between 220% of cases,[37] causing at least 200,000 deaths.[38] Cancers such as lung cancer and mesothelioma can come from inhaling tobacco smoke or asbestos fibers, or leukemia from exposure to benzene.[38]

Diet, physical inactivity and obesity are related to up to 3035% of cancer deaths.[5][39] In the United States excess body weight is associated with the development of many types of cancer and is a factor in 1420% of cancer deaths.[39] A UK study including data on over 5 million people showed higher body mass index to be related to at least 10 types of cancer and responsible for around 12,000 cases each year in that country.[40] Physical inactivity is believed to contribute to cancer risk, not only through its effect on body weight but also through negative effects on the immune system and endocrine system.[39] More than half of the effect from diet is due to overnutrition (eating too much), rather than from eating too few vegetables or other healthful foods.

Some specific foods are linked to specific cancers. A high-salt diet is linked to gastric cancer.[41]Aflatoxin B1, a frequent food contaminant, causes liver cancer.[41]Betel nut chewing can cause oral cancer.[41] National differences in dietary practices may partly explain differences in cancer incidence. For example, gastric cancer is more common in Japan due to its high-salt diet[42] while colon cancer is more common in the United States. Immigrant cancer profiles develop mirror that of their new country, often within one generation.[43]

Worldwide approximately 18% of cancer deaths are related to infectious diseases.[5] This proportion ranges from a high of 25% in Africa to less than 10% in the developed world.[5]Viruses are the usual infectious agents that cause cancer but cancer bacteria and parasites may also play a role.

Oncoviruses (viruses that can cause cancer) include human papillomavirus (cervical cancer), EpsteinBarr virus (B-cell lymphoproliferative disease and nasopharyngeal carcinoma), Kaposi's sarcoma herpesvirus (Kaposi's sarcoma and primary effusion lymphomas), hepatitis B and hepatitis C viruses (hepatocellular carcinoma) and human T-cell leukemia virus-1 (T-cell leukemias). Bacterial infection may also increase the risk of cancer, as seen in Helicobacter pylori-induced gastric carcinoma.[44][45] Parasitic infections associated with cancer include Schistosoma haematobium (squamous cell carcinoma of the bladder) and the liver flukes, Opisthorchis viverrini and Clonorchis sinensis (cholangiocarcinoma).[46]

Up to 10% of invasive cancers are related to radiation exposure, including both ionizing radiation and non-ionizing ultraviolet radiation.[5] Additionally, the majority of non-invasive cancers are non-melanoma skin cancers caused by non-ionizing ultraviolet radiation, mostly from sunlight. Sources of ionizing radiation include medical imaging and radon gas.

Ionizing radiation is not a particularly strong mutagen.[47] Residential exposure to radon gas, for example, has similar cancer risks as passive smoking.[47] Radiation is a more potent source of cancer when combined with other cancer-causing agents, such as radon plus tobacco smoke.[47] Radiation can cause cancer in most parts of the body, in all animals and at any age. Children and adolescents are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.[47]

Medical use of ionizing radiation is a small but growing source of radiation-induced cancers. Ionizing radiation may be used to treat other cancers, but this may, in some cases, induce a second form of cancer.[47] It is also used in some kinds of medical imaging.[48]

Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies.[49] Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.[49]

Non-ionizing radio frequency radiation from mobile phones, electric power transmission and other similar sources have been described as a possible carcinogen by the World Health Organization's International Agency for Research on Cancer.[50] However, studies have not found a consistent link between mobile phone radiation and cancer risk.[51]

The vast majority of cancers are non-hereditary ("sporadic"). Hereditary cancers are primarily caused by an inherited genetic defect. Less than 0.3% of the population are carriers of a genetic mutation that has a large effect on cancer risk and these cause less than 310% of cancer.[52] Some of these syndromes include: certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer,[52] and hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome), which is present in about 3% of people with colorectal cancer,[53] among others.

Some substances cause cancer primarily through their physical, rather than chemical, effects.[54] A prominent example of this is prolonged exposure to asbestos, naturally occurring mineral fibers that are a major cause of mesothelioma (cancer of the serous membrane) usually the serous membrane surrounding the lungs.[54] Other substances in this category, including both naturally occurring and synthetic asbestos-like fibers, such as wollastonite, attapulgite, glass wool and rock wool, are believed to have similar effects.[54] Non-fibrous particulate materials that cause cancer include powdered metallic cobalt and nickel and crystalline silica (quartz, cristobalite and tridymite).[54] Usually, physical carcinogens must get inside the body (such as through inhalation) and require years of exposure to produce cancer.[54]

Physical trauma resulting in cancer is relatively rare.[55] Claims that breaking bones resulted in bone cancer, for example, have not been proven.[55] Similarly, physical trauma is not accepted as a cause for cervical cancer, breast cancer or brain cancer.[55] One accepted source is frequent, long-term application of hot objects to the body. It is possible that repeated burns on the same part of the body, such as those produced by kanger and kairo heaters (charcoal hand warmers), may produce skin cancer, especially if carcinogenic chemicals are also present.[55] Frequent consumption of scalding hot tea may produce esophageal cancer.[55] Generally, it is believed that the cancer arises, or a pre-existing cancer is encouraged, during the process of healing, rather than directly by the trauma.[55] However, repeated injuries to the same tissues might promote excessive cell proliferation, which could then increase the odds of a cancerous mutation.

Chronic inflammation has been hypothesized to directly cause mutation.[55][56] Inflammation can contribute to proliferation, survival, angiogenesis and migration of cancer cells by influencing the tumor microenvironment.[57][58]Oncogenes build up an inflammatory pro-tumorigenic microenvironment.[59]

Some hormones play a role in the development of cancer by promoting cell proliferation.[60]Insulin-like growth factors and their binding proteins play a key role in cancer cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis.[61]

Hormones are important agents in sex-related cancers, such as cancer of the breast, endometrium, prostate, ovary and testis and also of thyroid cancer and bone cancer.[60] For example, the daughters of women who have breast cancer have significantly higher levels of estrogen and progesterone than the daughters of women without breast cancer. These higher hormone levels may explain their higher risk of breast cancer, even in the absence of a breast-cancer gene.[60] Similarly, men of African ancestry have significantly higher levels of testosterone than men of European ancestry and have a correspondingly higher level of prostate cancer.[60] Men of Asian ancestry, with the lowest levels of testosterone-activating androstanediol glucuronide, have the lowest levels of prostate cancer.[60]

Other factors are relevant: obese people have higher levels of some hormones associated with cancer and a higher rate of those cancers.[60] Women who take hormone replacement therapy have a higher risk of developing cancers associated with those hormones.[60] On the other hand, people who exercise far more than average have lower levels of these hormones and lower risk of cancer.[60]Osteosarcoma may be promoted by growth hormones.[60] Some treatments and prevention approaches leverage this cause by artificially reducing hormone levels and thus discouraging hormone-sensitive cancers.[60]

There is an association between celiac disease and an increased risk of all cancers. People with untreated celiac disease have a higher risk, but this risk decreases with time after diagnosis and strict treatment, probably due to the adoption of a gluten-free diet, which seems to have a protective role against development of malignancy in people with celiac disease. However, the delay in diagnosis and initiation of a gluten-free diet seems to increase the risk of malignancies.[62] Rates of gastrointestinal cancers are increased in people with Crohn's disease and ulcerative colitis, due to chronic inflammation. Also, immunomodulators and biologic agents used to treat these diseases may promote developing extra-intestinal malignancies.[63]

Cancer is fundamentally a disease of tissue growth regulation. In order for a normal cell to transform into a cancer cell, the genes that regulate cell growth and differentiation must be altered.[64]

The affected genes are divided into two broad categories. Oncogenes are genes that promote cell growth and reproduction. Tumor suppressor genes are genes that inhibit cell division and survival. Malignant transformation can occur through the formation of novel oncogenes, the inappropriate over-expression of normal oncogenes, or by the under-expression or disabling of tumor suppressor genes. Typically, changes in multiple genes are required to transform a normal cell into a cancer cell.[65]

Genetic changes can occur at different levels and by different mechanisms. The gain or loss of an entire chromosome can occur through errors in mitosis. More common are mutations, which are changes in the nucleotide sequence of genomic DNA.

Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains copies (often 20 or more) of a small chromosomal locus, usually containing one or more oncogenes and adjacent genetic material. Translocation occurs when two separate chromosomal regions become abnormally fused, often at a characteristic location. A well-known example of this is the Philadelphia chromosome, or translocation of chromosomes 9 and 22, which occurs in chronic myelogenous leukemia and results in production of the BCR-abl fusion protein, an oncogenic tyrosine kinase.

Small-scale mutations include point mutations, deletions and insertions, which may occur in the promoter region of a gene and affect its expression, or may occur in the gene's coding sequence and alter the function or stability of its protein product. Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, leading to the expression of viral oncogenes in the affected cell and its descendants.

Replication of the data contained within the DNA of living cells will probabilistically result in some errors (mutations). Complex error correction and prevention is built into the process and safeguards the cell against cancer. If significant error occurs, the damaged cell can self-destruct through programmed cell death, termed apoptosis. If the error control processes fail, then the mutations will survive and be passed along to daughter cells.

Some environments make errors more likely to arise and propagate. Such environments can include the presence of disruptive substances called carcinogens, repeated physical injury, heat, ionising radiation or hypoxia.[66]

The errors that cause cancer are self-amplifying and compounding, for example:

The transformation of a normal cell into cancer is akin to a chain reaction caused by initial errors, which compound into more severe errors, each progressively allowing the cell to escape more controls that limit normal tissue growth. This rebellion-like scenario is an undesirable survival of the fittest, where the driving forces of evolution work against the body's design and enforcement of order. Once cancer has begun to develop, this ongoing process, termed clonal evolution, drives progression towards more invasive stages.[67] Clonal evolution leads to intra-tumour heterogeneity (cancer cells with heterogeneous mutations) that complicates designing effective treatment strategies.

Characteristic abilities developed by cancers are divided into categories, specifically evasion of apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth signals, sustained angiogenesis, limitless replicative potential, metastasis, reprogramming of energy metabolism and evasion of immune destruction.[24][25]

The classical view of cancer is a set of diseases that are driven by progressive genetic abnormalities that include mutations in tumor-suppressor genes and oncogenes and chromosomal abnormalities. Later epigenetic alterations' role was identified.[68]

Epigenetic alterations refer to functionally relevant modifications to the genome that do not change the nucleotide sequence. Examples of such modifications are changes in DNA methylation (hypermethylation and hypomethylation), histone modification[69] and changes in chromosomal architecture (caused by inappropriate expression of proteins such as HMGA2 or HMGA1).[70] Each of these alterations regulates gene expression without altering the underlying DNA sequence. These changes may remain through cell divisions, last for multiple generations and can be considered to be epimutations (equivalent to mutations).

Epigenetic alterations occur frequently in cancers. As an example, one study listed protein coding genes that were frequently altered in their methylation in association with colon cancer. These included 147 hypermethylated and 27 hypomethylated genes. Of the hypermethylated genes, 10 were hypermethylated in 100% of colon cancers and many others were hypermethylated in more than 50% of colon cancers.[71]

While epigenetic alterations are found in cancers, the epigenetic alterations in DNA repair genes, causing reduced expression of DNA repair proteins, may be of particular importance. Such alterations are thought to occur early in progression to cancer and to be a likely cause of the genetic instability characteristic of cancers.[72][73][74][75]

Reduced expression of DNA repair genes disrupts DNA repair. This is shown in the figure at the 4th level from the top. (In the figure, red wording indicates the central role of DNA damage and defects in DNA repair in progression to cancer.) When DNA repair is deficient DNA damage remains in cells at a higher than usual level (5th level) and cause increased frequencies of mutation and/or epimutation (6th level). Mutation rates increase substantially in cells defective in DNA mismatch repair[76][77] or in homologous recombinational repair (HRR).[78] Chromosomal rearrangements and aneuploidy also increase in HRR defective cells.[79]

Higher levels of DNA damage cause increased mutation (right side of figure) and increased epimutation. During repair of DNA double strand breaks, or repair of other DNA damage, incompletely cleared repair sites can cause epigenetic gene silencing.[80][81]

Deficient expression of DNA repair proteins due to an inherited mutation can increase cancer risks. Individuals with an inherited impairment in any of 34 DNA repair genes (see article DNA repair-deficiency disorder) have increased cancer risk, with some defects ensuring a 100% lifetime chance of cancer (e.g. p53 mutations).[82] Germ line DNA repair mutations are noted on the figure's left side. However, such germline mutations (which cause highly penetrant cancer syndromes) are the cause of only about 1 percent of cancers.[83]

In sporadic cancers, deficiencies in DNA repair are occasionally caused by a mutation in a DNA repair gene, but are much more frequently caused by epigenetic alterations that reduce or silence expression of DNA repair genes. This is indicated in the figure at the 3rd level. Many studies of heavy metal-induced carcinogenesis show that such heavy metals cause reduction in expression of DNA repair enzymes, some through epigenetic mechanisms. DNA repair inhibition is proposed to be a predominant mechanism in heavy metal-induced carcinogenicity. In addition, frequent epigenetic alterations of the DNA sequences code for small RNAs called microRNAs (or miRNAs). MiRNAs do not code for proteins, but can "target" protein-coding genes and reduce their expression.

Cancers usually arise from an assemblage of mutations and epimutations that confer a selective advantage leading to clonal expansion (see Field defects in progression to cancer). Mutations, however, may not be as frequent in cancers as epigenetic alterations. An average cancer of the breast or colon can have about 60 to 70 protein-altering mutations, of which about three or four may be "driver" mutations and the remaining ones may be "passenger" mutations.[84]

Metastasis is the spread of cancer to other locations in the body. The dispersed tumors are called metastatic tumors, while the original is called the primary tumor. Almost all cancers can metastasize.[85] Most cancer deaths are due to cancer that has metastasized.[86]

Metastasis is common in the late stages of cancer and it can occur via the blood or the lymphatic system or both. The typical steps in metastasis are local invasion, intravasation into the blood or lymph, circulation through the body, extravasation into the new tissue, proliferation and angiogenesis. Different types of cancers tend to metastasize to particular organs, but overall the most common places for metastases to occur are the lungs, liver, brain and the bones.[85]

Most cancers are initially recognized either because of the appearance of signs or symptoms or through screening. Neither of these lead to a definitive diagnosis, which requires the examination of a tissue sample by a pathologist. People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, CT scans and endoscopy.

People may become extremely anxious and depressed post-diagnosis. The risk of suicide in people with cancer is approximately double the normal risk.[87]

Cancers are classified by the type of cell that the tumor cells resemble and is therefore presumed to be the origin of the tumor. These types include:

Cancers are usually named using -carcinoma, -sarcoma or -blastoma as a suffix, with the Latin or Greek word for the organ or tissue of origin as the root. For example, cancers of the liver parenchyma arising from malignant epithelial cells is called hepatocarcinoma, while a malignancy arising from primitive liver precursor cells is called a hepatoblastoma and a cancer arising from fat cells is called a liposarcoma. For some common cancers, the English organ name is used. For example, the most common type of breast cancer is called ductal carcinoma of the breast. Here, the adjective ductal refers to the appearance of the cancer under the microscope, which suggests that it has originated in the milk ducts.

Benign tumors (which are not cancers) are named using -oma as a suffix with the organ name as the root. For example, a benign tumor of smooth muscle cells is called a leiomyoma (the common name of this frequently occurring benign tumor in the uterus is fibroid). Confusingly, some types of cancer use the -noma suffix, examples including melanoma and seminoma.

Some types of cancer are named for the size and shape of the cells under a microscope, such as giant cell carcinoma, spindle cell carcinoma and small-cell carcinoma.

The tissue diagnosis from the biopsy indicates the type of cell that is proliferating, its histological grade, genetic abnormalities and other features. Together, this information is useful to evaluate the prognosis of the patient and to choose the best treatment. Cytogenetics and immunohistochemistry are other types of tissue tests. These tests may provide information about molecular changes (such as mutations, fusion genes and numerical chromosome changes) and may thus also indicate the prognosis and best treatment.

Cancer prevention is defined as active measures to decrease cancer risk.[89] The vast majority of cancer cases are due to environmental risk factors. Many of these environmental factors are controllable lifestyle choices. Thus, cancer is generally preventable.[90] Between 70% and 90% of common cancers are due to environmental factors and therefore potentially preventable.[91]

Greater than 30% of cancer deaths could be prevented by avoiding risk factors including: tobacco, excess weight/obesity, insufficient diet, physical inactivity, alcohol, sexually transmitted infections and air pollution.[92] Not all environmental causes are controllable, such as naturally occurring background radiation and cancers caused through hereditary genetic disorders and thus are not preventable via personal behavior.

While many dietary recommendations have been proposed to reduce cancer risks, the evidence to support them is not definitive.[9][93] The primary dietary factors that increase risk are obesity and alcohol consumption. Diets low in fruits and vegetables and high in red meat have been implicated but reviews and meta-analyses do not come to a consistent conclusion.[94][95] A 2014 meta-analysis find no relationship between fruits and vegetables and cancer.[96]Coffee is associated with a reduced risk of liver cancer.[97] Studies have linked excess consumption of red or processed meat to an increased risk of breast cancer, colon cancer and pancreatic cancer, a phenomenon that could be due to the presence of carcinogens in meats cooked at high temperatures.[98][99] In 2015 the IARC reported that eating processed meat (e.g., bacon, ham, hot dogs, sausages) and, to a lesser degree, red meat was linked to some cancers.[100][101]

Dietary recommendations for cancer prevention typically include an emphasis on vegetables, fruit, whole grains and fish and an avoidance of processed and red meat (beef, pork, lamb), animal fats and refined carbohydrates.[9][93]

Medications can be used to prevent cancer in a few circumstances.[102] In the general population, NSAIDs reduce the risk of colorectal cancer; however, due to cardiovascular and gastrointestinal side effects, they cause overall harm when used for prevention.[103]Aspirin has been found to reduce the risk of death from cancer by about 7%.[104]COX-2 inhibitors may decrease the rate of polyp formation in people with familial adenomatous polyposis; however, it is associated with the same adverse effects as NSAIDs.[105] Daily use of tamoxifen or raloxifene reduce the risk of breast cancer in high-risk women.[106] The benefit versus harm for 5-alpha-reductase inhibitor such as finasteride is not clear.[107]

Vitamins are not effective at preventing cancer,[108] although low blood levels of vitamin D are correlated with increased cancer risk.[109][110] Whether this relationship is causal and vitamin D supplementation is protective is not determined.[111]Beta-carotene supplementation increases lung cancer rates in those who are high risk.[112]Folic acid supplementation is not effective in preventing colon cancer and may increase colon polyps.[113] It is unclear if selenium supplementation has an effect.[114]

Vaccines have been developed that prevent infection by some carcinogenic viruses.[115]Human papillomavirus vaccine (Gardasil and Cervarix) decrease the risk of developing cervical cancer.[115] The hepatitis B vaccine prevents infection with hepatitis B virus and thus decreases the risk of liver cancer.[115] The administration of human papillomavirus and hepatitis B vaccinations is recommended when resources allow.[116]

Unlike diagnostic efforts prompted by symptoms and medical signs, cancer screening involves efforts to detect cancer after it has formed, but before any noticeable symptoms appear.[117] This may involve physical examination, blood or urine tests or medical imaging.[117]

Cancer screening is not available for many types of cancers. Even when tests are available, they may not be recommended for everyone. Universal screening or mass screening involves screening everyone.[118]Selective screening identifies people who are at higher risk, such as people with a family history.[118] Several factors are considered to determine whether the benefits of screening outweigh the risks and the costs of screening.[117] These factors include:

The U.S. Preventive Services Task Force (USPSTF) issues recommendations for various cancers:

Screens for gastric cancer using photofluorography due to the high incidence there.[19]

Genetic testing for individuals at high-risk of certain cancers is recommended by unofficial groups.[116][132] Carriers of these mutations may then undergo enhanced surveillance, chemoprevention, or preventative surgery to reduce their subsequent risk.[132]

Many treatment options for cancer exist. The primary ones include surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy and palliative care. Which treatments are used depends on the type, location and grade of the cancer as well as the patient's health and preferences. The treatment intent may or may not be curative.

Chemotherapy is the treatment of cancer with one or more cytotoxic anti-neoplastic drugs (chemotherapeutic agents) as part of a standardized regimen. The term encompasses a variety of drugs, which are divided into broad categories such as alkylating agents and antimetabolites.[133] Traditional chemotherapeutic agents act by killing cells that divide rapidly, a critical property of most cancer cells.

Targeted therapy is a form of chemotherapy that targets specific molecular differences between cancer and normal cells. The first targeted therapies blocked the estrogen receptor molecule, inhibiting the growth of breast cancer. Another common example is the class of Bcr-Abl inhibitors, which are used to treat chronic myelogenous leukemia (CML).[134] Currently, targeted therapies exist for breast cancer, multiple myeloma, lymphoma, prostate cancer, melanoma and other cancers.[135]

The efficacy of chemotherapy depends on the type of cancer and the stage. In combination with surgery, chemotherapy has proven useful in cancer types including breast cancer, colorectal cancer, pancreatic cancer, osteogenic sarcoma, testicular cancer, ovarian cancer and certain lung cancers.[136] Chemotherapy is curative for some cancers, such as some leukemias,[137][138] ineffective in some brain tumors,[139] and needless in others, such as most non-melanoma skin cancers.[140] The effectiveness of chemotherapy is often limited by its toxicity to other tissues in the body. Even when chemotherapy does not provide a permanent cure, it may be useful to reduce symptoms such as pain or to reduce the size of an inoperable tumor in the hope that surgery will become possible in the future.

Radiation therapy involves the use of ionizing radiation in an attempt to either cure or improve symptoms. It works by damaging the DNA of cancerous tissue, killing it. To spare normal tissues (such as skin or organs, which radiation must pass through to treat the tumor), shaped radiation beams are aimed from multiple exposure angles to intersect at the tumor, providing a much larger dose there than in the surrounding, healthy tissue. As with chemotherapy, cancers vary in their response to radiation therapy.[141][142][143]

Radiation therapy is used in about half of cases. The radiation can be either from internal sources (brachytherapy) or external sources. The radiation is most commonly low energy x-rays for treating skin cancers, while higher energy x-rays are used for cancers within the body.[144] Radiation is typically used in addition to surgery and or chemotherapy. For certain types of cancer, such as early head and neck cancer, it may be used alone.[145] For painful bone metastasis, it has been found to be effective in about 70% of patients.[145]

Surgery is the primary method of treatment for most isolated, solid cancers and may play a role in palliation and prolongation of survival. It is typically an important part of definitive diagnosis and staging of tumors, as biopsies are usually required. In localized cancer, surgery typically attempts to remove the entire mass along with, in certain cases, the lymph nodes in the area. For some types of cancer this is sufficient to eliminate the cancer.[136]

Palliative care refers to treatment that attempts to help the patient feel better and may be combined with an attempt to treat the cancer. Palliative care includes action to reduce physical, emotional, spiritual and psycho-social distress. Unlike treatment that is aimed at directly killing cancer cells, the primary goal of palliative care is to improve quality of life.

People at all stages of cancer treatment typically receive some kind of palliative care. In some cases, medical specialty professional organizations recommend that patients and physicians respond to cancer only with palliative care.[146] This applies to patients who:[147]

Palliative care may be confused with hospice and therefore only indicated when people approach end of life. Like hospice care, palliative care attempts to help the patient cope with their immediate needs and to increase comfort. Unlike hospice care, palliative care does not require people to stop treatment aimed.

Multiple national medical guidelines recommend early palliative care for patients whose cancer has produced distressing symptoms or who need help coping with their illness. In patients first diagnosed with metastatic disease, palliative care may be immediately indicated. Palliative care is indicated for patients with a prognosis of less than 12 months of life even given aggressive treatment.[148][149][150]

A variety of therapies using immunotherapy, stimulating or helping the immune system to fight cancer, have come into use since 1997. Approaches include antibodies, checkpoint therapy and adoptive cell transfer.[151]

Complementary and alternative cancer treatments are a diverse group of therapies, practices and products that are not part of conventional medicine.[152] "Complementary medicine" refers to methods and substances used along with conventional medicine, while "alternative medicine" refers to compounds used instead of conventional medicine.[153] Most complementary and alternative medicines for cancer have not been studied or tested using conventional techniques such as clinical trials. Some alternative treatments have been investigated and shown to be ineffective but still continue to be marketed and promoted. Cancer researcher Andrew J. Vickers stated, "The label 'unproven' is inappropriate for such therapies; it is time to assert that many alternative cancer therapies have been 'disproven'."[154]

Survival rates vary by cancer type and by the stage at which it is diagnosed, ranging from majority survival to complete mortality five years after diagnosis. Once a cancer has metastasized, prognosis normally becomes much worse. About half of patients receiving treatment for invasive cancer (excluding carcinoma in situ and non-melanoma skin cancers) die from that cancer or its treatment.[19]

Survival is worse in the developing world,[19] partly because the types of cancer that are most common there are harder to treat than those associated with developed countries.[155]

Those who survive cancer develop a second primary cancer at about twice the rate of those never diagnosed.[156] The increased risk is believed to be primarily due to the same risk factors that produced the first cancer, partly due to treatment of the first cancer and to better compliance with screening.[156]

Predicting short- or long-term survival depends on many factors. The most important are the cancer type and the patient's age and overall health. Those who are frail with other health problems have lower survival rates than otherwise healthy people. Centenarians are unlikely to survive for five years even if treatment is successful. People who report a higher quality of life tend to survive longer.[157] People with lower quality of life may be affected by depression and other complications and/or disease progression that both impairs quality and quantity of life. Additionally, patients with worse prognoses may be depressed or report poorer quality of life because they perceive that their condition is likely to be fatal.

Cancer patients have an increased risk of blood clots in veins. The use of heparin appears to improve survival and decrease the risk of blood clots.[158]

135-367

368-443

444-521

522-588

589-736

737-968

969-1,567

Go here to read the rest:
Cancer - Wikipedia

Stem-cell therapy – Wikipedia

By adminOctober 19, 2016Embryonic Stem Cells

This article is about the medical therapy. For the cell type, see Stem cell.

Stem-cell therapy is the use of stem cells to treat or prevent a disease or condition.

Bone marrow transplant is the most widely used stem-cell therapy, but some therapies derived from umbilical cord blood are also in use. Research is underway to develop various sources for stem cells, and to apply stem-cell treatments for neurodegenerative diseases and conditions such as diabetes, heart disease, and other conditions.

Stem-cell therapy has become controversial following developments such as the ability of scientists to isolate and culture embryonic stem cells, to create stem cells using somatic cell nuclear transfer and their use of techniques to create induced pluripotent stem cells. This controversy is often related to abortion politics and to human cloning. Additionally, efforts to market treatments based on transplant of stored umbilical cord blood have been controversial.

For over 30 years, bone marrow has been used to treat cancer patients with conditions such as leukaemia and lymphoma; this is the only form of stem-cell therapy that is widely practiced.[1][2][3] During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukaemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem-cell transplant attempts to reverse; a donor's healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host's body during treatment. The transplanted cells also generate an immune response that helps to kill off the cancer cells; this process can go too far, however, leading to graft vs host disease, the most serious side effect of this treatment.[4]

Another stem-cell therapy called Prochymal, was conditionally approved in Canada in 2012 for the management of acute graft-vs-host disease in children who are unresponsive to steroids.[5] It is an allogenic stem therapy based on mesenchymal stem cells (MSCs) derived from the bone marrow of adult donors. MSCs are purified from the marrow, cultured and packaged, with up to 10,000 doses derived from a single donor. The doses are stored frozen until needed.[6]

The FDA has approved five hematopoietic stem-cell products derived from umbilical cord blood, for the treatment of blood and immunological diseases.[7]

In 2014, the European Medicines Agency recommended approval of Holoclar, a treatment involving stem cells, for use in the European Union. Holoclar is used for people with severe limbal stem cell deficiency due to burns in the eye.[8]

In March 2016 GlaxoSmithKline's Strimvelis (GSK2696273) therapy for the treatment ADA-SCID was recommended for EU approval.[9]

Stem cells are being studied for a number of reasons. The molecules and exosomes released from stem cells are also being studied in an effort to make medications.[10]

Research has been conducted on the effects of stem cells on animal models of brain degeneration, such as in Parkinson's, Amyotrophic lateral sclerosis, and Alzheimer's disease.[11][12][13] There have been preliminary studies related to multiple sclerosis.[14][15]

Healthy adult brains contain neural stem cells which divide to maintain general stem-cell numbers, or become progenitor cells. In healthy adult laboratory animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). Pharmacological activation of endogenous neural stem cells has been reported to induce neuroprotection and behavioral recovery in adult rat models of neurological disorder.[16][17][18]

Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. A small clinical trial was underway in Scotland in 2013, in which stem cells were injected into the brains of stroke patients.[19]

Clinical and animal studies have been conducted into the use of stem cells in cases of spinal cord injury.[20][21][22]

The pioneering work[23] by Bodo-Eckehard Strauer has now been discredited by the identification of hundreds of factual contradictions.[24] Among several clinical trials that have reported that adult stem-cell therapy is safe and effective, powerful effects have been reported from only a few laboratories, but this has covered old[25] and recent[26] infarcts as well as heart failure not arising from myocardial infarction.[27] While initial animal studies demonstrated remarkable therapeutic effects,[28][29] later clinical trials achieved only modest, though statistically significant, improvements.[30][31] Possible reasons for this discrepancy are patient age,[32] timing of treatment[33] and the recent occurrence of a myocardial infarction.[34] It appears that these obstacles may be overcome by additional treatments which increase the effectiveness of the treatment[35] or by optimizing the methodology although these too can be controversial. Current studies vary greatly in cell-procuring techniques, cell types, cell-administration timing and procedures, and studied parameters, making it very difficult to make comparisons. Comparative studies are therefore currently needed.

Stem-cell therapy for treatment of myocardial infarction usually makes use of autologous bone-marrow stem cells (a specific type or all), however other types of adult stem cells may be used, such as adipose-derived stem cells.[36] Adult stem cell therapy for treating heart disease was commercially available in at least five continents as of 2007.[citation needed]

Possible mechanisms of recovery include:[11]

It may be possible to have adult bone-marrow cells differentiate into heart muscle cells.[11]

The first successful integration of human embryonic stem cell derived cardiomyocytes in guinea pigs (mouse hearts beat too fast) was reported in August 2012. The contraction strength was measured four weeks after the guinea pigs underwent simulated heart attacks and cell treatment. The cells contracted synchronously with the existing cells, but it is unknown if the positive results were produced mainly from paracrine as opposed to direct electromechanical effects from the human cells. Future work will focus on how to get the cells to engraft more strongly around the scar tissue. Whether treatments from embryonic or adult bone marrow stem cells will prove more effective remains to be seen.[37]

In 2013 the pioneering reports of powerful beneficial effects of autologous bone marrow stem cells on ventricular function were found to contain "hundreds" of discrepancies.[38] Critics report that of 48 reports there seemed to be just five underlying trials, and that in many cases whether they were randomized or merely observational accepter-versus-rejecter, was contradictory between reports of the same trial. One pair of reports of identical baseline characteristics and final results, was presented in two publications as, respectively, a 578 patient randomized trial and as a 391 patient observational study. Other reports required (impossible) negative standard deviations in subsets of patients, or contained fractional patients, negative NYHA classes. Overall there were many more patients published as having receiving stem cells in trials, than the number of stem cells processed in the hospital's laboratory during that time. A university investigation, closed in 2012 without reporting, was reopened in July 2013.[39]

One of the most promising benefits of stem cell therapy is the potential for cardiac tissue regeneration to reverse the tissue loss underlying the development of heart failure after cardiac injury.[40]

Initially, the observed improvements were attributed to a transdifferentiation of BM-MSCs into cardiomyocyte-like cells.[28] Given the apparent inadequacy of unmodified stem cells for heart tissue regeneration, a more promising modern technique involves treating these cells to create cardiac progenitor cells before implantation to the injured area.[41]

The specificity of the human immune-cell repertoire is what allows the human body to defend itself from rapidly adapting antigens. However, the immune system is vulnerable to degradation upon the pathogenesis of disease, and because of the critical role that it plays in overall defense, its degradation is often fatal to the organism as a whole. Diseases of hematopoietic cells are diagnosed and classified via a subspecialty of pathology known as hematopathology. The specificity of the immune cells is what allows recognition of foreign antigens, causing further challenges in the treatment of immune disease. Identical matches between donor and recipient must be made for successful transplantation treatments, but matches are uncommon, even between first-degree relatives. Research using both hematopoietic adult stem cells and embryonic stem cells has provided insight into the possible mechanisms and methods of treatment for many of these ailments.[citation needed]

Fully mature human red blood cells may be generated ex vivo by hematopoietic stem cells (HSCs), which are precursors of red blood cells. In this process, HSCs are grown together with stromal cells, creating an environment that mimics the conditions of bone marrow, the natural site of red-blood-cell growth. Erythropoietin, a growth factor, is added, coaxing the stem cells to complete terminal differentiation into red blood cells.[42] Further research into this technique should have potential benefits to gene therapy, blood transfusion, and topical medicine.

In 2004, scientists at King's College London discovered a way to cultivate a complete tooth in mice[43] and were able to grow bioengineered teeth stand-alone in the laboratory. Researchers are confident that the tooth regeneration technology can be used to grow live teeth in human patients.

In theory, stem cells taken from the patient could be coaxed in the lab turning into a tooth bud which, when implanted in the gums, will give rise to a new tooth, and would be expected to be grown in a time over three weeks.[44] It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth. Many challenges remain, however, before stem cells could be a choice for the replacement of missing teeth in the future.[45][46]

Research is ongoing in different fields, alligators which are polyphyodonts grow up to 50 times a successional tooth (a small replacement tooth) under each mature functional tooth for replacement once a year.[47]

Heller has reported success in re-growing cochlea hair cells with the use of embryonic stem cells.[48]

Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. "Sheets of retinal cells used by the team are harvested from aborted fetuses, which some people find objectionable." When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restore vision.[49] The latest such development was in June 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty patients using the same technique. The group, led by Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver. Further rounds of trials are ongoing.[50]

In April 2005, doctors in the UK transplanted corneal stem cells from an organ donor to the cornea of Deborah Catlyn, a woman who was blinded in one eye when acid was thrown in her eye at a nightclub. The cornea, which is the transparent window of the eye, is a particularly suitable site for transplants. In fact, the first successful human transplant was a cornea transplant. The absence of blood vessels within the cornea makes this area a relatively easy target for transplantation. The majority of corneal transplants carried out today are due to a degenerative disease called keratoconus.

The University Hospital of New Jersey reports that the success rate for growth of new cells from transplanted stem cells varies from 25 percent to 70 percent.[51]

In 2014, researchers demonstrated that stem cells collected as biopsies from donor human corneas can prevent scar formation without provoking a rejection response in mice with corneal damage.[52]

In January 2012, The Lancet published a paper by Steven Schwartz, at UCLA's Jules Stein Eye Institute, reporting two women who had gone legally blind from macular degeneration had dramatic improvements in their vision after retinal injections of human embryonic stem cells.[53]

In June 2015, the Stem Cell Ophthalmology Treatment Study (SCOTS), the largest adult stem cell study in ophthalmology ( http://www.clinicaltrials.gov NCT # 01920867) published initial results on a patient with optic nerve disease who improved from 20/2000 to 20/40 following treatment with bone marrow derived stem cells.[54]

Diabetes patients lose the function of insulin-producing beta cells within the pancreas.[55] In recent experiments, scientists have been able to coax embryonic stem cell to turn into beta cells in the lab. In theory if the beta cell is transplanted successfully, they will be able to replace malfunctioning ones in a diabetic patient.[56]

Human embryonic stem cells may be grown in cell culture and stimulated to form insulin-producing cells that can be transplanted into the patient.

However, clinical success is highly dependent on the development of the following procedures:[11]

Clinical case reports in the treatment orthopaedic conditions have been reported. To date, the focus in the literature for musculoskeletal care appears to be on mesenchymal stem cells. Centeno et al. have published MRI evidence of increased cartilage and meniscus volume in individual human subjects.[57][58] The results of trials that include a large number of subjects, are yet to be published. However, a published safety study conducted in a group of 227 patients over a 3-4-year period shows adequate safety and minimal complications associated with mesenchymal cell transplantation.[59]

Wakitani has also published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.[60]

Stem cells can also be used to stimulate the growth of human tissues. In an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. In the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells.[61] A possible method for tissue regeneration in adults is to place adult stem cell "seeds" inside a tissue bed "soil" in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method elicits a regenerative response more similar to fetal wound-healing than adult scar tissue formation.[61] Researchers are still investigating different aspects of the "soil" tissue that are conducive to regeneration.[61]

Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells (precursor cells of oocytes and spermatozoa), as evidenced by gene expression analysis.[62]

Human embryonic stem cells have been stimulated to form Spermatozoon-like cells, yet still slightly damaged or malformed.[63] It could potentially treat azoospermia.

In 2012, oogonial stem cells were isolated from adult mouse and human ovaries and demonstrated to be capable of forming mature oocytes.[64] These cells have the potential to treat infertility.

Destruction of the immune system by the HIV is driven by the loss of CD4+ T cells in the peripheral blood and lymphoid tissues. Viral entry into CD4+ cells is mediated by the interaction with a cellular chemokine receptor, the most common of which are CCR5 and CXCR4. Because subsequent viral replication requires cellular gene expression processes, activated CD4+ cells are the primary targets of productive HIV infection.[65] Recently scientists have been investigating an alternative approach to treating HIV-1/AIDS, based on the creation of a disease-resistant immune system through transplantation of autologous, gene-modified (HIV-1-resistant) hematopoietic stem and progenitor cells (GM-HSPC).[66]

On 23 January 2009, the US Food and Drug Administration gave clearance to Geron Corporation for the initiation of the first clinical trial of an embryonic stem-cell-based therapy on humans. The trial aimed evaluate the drug GRNOPC1, embryonic stem cell-derived oligodendrocyte progenitor cells, on patients with acute spinal cord injury. The trial was discontinued in November 2011 so that the company could focus on therapies in the "current environment of capital scarcity and uncertain economic conditions".[67] In 2013 biotechnology and regenerative medicine company BioTime (NYSEMKT:BTX) acquired Geron's stem cell assets in a stock transaction, with the aim of restarting the clinical trial.[68]

Scientists have reported that MSCs when transfused immediately within few hours post thawing may show reduced function or show decreased efficacy in treating diseases as compared to those MSCs which are in log phase of cell growth(fresh), so cryopreserved MSCs should be brought back into log phase of cell growth in invitro culture before these are administered for clinical trials or experimental therapies, re-culturing of MSCs will help in recovering from the shock the cells get during freezing and thawing. Various clinical trials on MSCs have failed which used cryopreserved product immediately post thaw as compared to those clinical trials which used fresh MSCs.[69]

Research currently conducted on horses, dogs, and cats can benefit the development of stem cell treatments in veterinary medicine and can target a wide range of injuries and diseases such as myocardial infarction, stroke, tendon and ligament damage, osteoarthritis, osteochondrosis and muscular dystrophy both in large animals, as well as humans.[70][71][72][73] While investigation of cell-based therapeutics generally reflects human medical needs, the high degree of frequency and severity of certain injuries in racehorses has put veterinary medicine at the forefront of this novel regenerative approach.[74] Companion animals can serve as clinically relevant models that closely mimic human disease.[75][76]

There is widespread controversy over the use of human embryonic stem cells. This controversy primarily targets the techniques used to derive new embryonic stem cell lines, which often requires the destruction of the blastocyst. Opposition to the use of human embryonic stem cells in research is often based on philosophical, moral, or religious objections.[110] There is other stem cell research that does not involve the destruction of a human embryo, and such research involves adult stem cells, amniotic stem cells, and induced pluripotent stem cells.

Stem-cell research and treatment was practiced in the People's Republic of China. The Ministry of Health of the People's Republic of China has permitted the use of stem-cell therapy for conditions beyond those approved of in Western countries. The Western World has scrutinized China for its failed attempts to meet international documentation standards of these trials and procedures.[111]

State-funded companies based in the Shenzhen Hi-Tech Industrial Zone treat the symptoms of numerous disorders with adult stem-cell therapy. Development companies are currently focused on the treatment of neurodegenerative and cardiovascular disorders. The most radical successes of Chinese adult stem cell therapy have been in treating the brain. These therapies administer stem cells directly to the brain of patients with cerebral palsy, Alzheimer's, and brain injuries.[citation needed]

Since 2008 many universities, centers and doctors tried a diversity of methods; in Lebanon proliferation for stem cell therapy, in-vivo and in-vitro techniques were used, Thus this country is considered the launching place of the Regentime[112] procedure. http://www.researchgate.net/publication/281712114_Treatment_of_Long_Standing_Multiple_Sclerosis_with_Regentime_Stem_Cell_Technique The regenerative medicine also took place in Jordan and Egypt.[citation needed]

Stem-cell treatment is currently being practiced at a clinical level in Mexico. An International Health Department Permit (COFEPRIS) is required. Authorized centers are found in Tijuana, Guadalajara and Cancun. Currently undergoing the approval process is Los Cabos. This permit allows the use of stem cell.[citation needed]

In 2005, South Korean scientists claimed to have generated stem cells that were tailored to match the recipient. Each of the 11 new stem cell lines was developed using somatic cell nuclear transfer (SCNT) technology. The resultant cells were thought to match the genetic material of the recipient, thus suggesting minimal to no cell rejection.[113]

As of 2013, Thailand still considers Hematopoietic stem cell transplants as experimental. Kampon Sriwatanakul began with a clinical trial in October 2013 with 20 patients. 10 are going to receive stem-cell therapy for Type-2 diabetes and the other 10 will receive stem-cell therapy for emphysema. Chotinantakul's research is on Hematopoietic cells and their role for the hematopoietic system function in homeostasis and immune response.[114]

Today, Ukraine is permitted to perform clinical trials of stem-cell treatments (Order of the MH of Ukraine 630 "About carrying out clinical trials of stem cells", 2008) for the treatment of these pathologies: pancreatic necrosis, cirrhosis, hepatitis, burn disease, diabetes, multiple sclerosis, critical lower limb ischemia. The first medical institution granted the right to conduct clinical trials became the "Institute of Cell Therapy"(Kiev).

Other countries where doctors did stem cells research, trials, manipulation, storage, therapy: Brazil, Cyprus, Germany, Italy, Israel, Japan, Pakistan, Philippines, Russia, Switzerland, Turkey, United Kingdom, India, and many others.

See original here:
Stem-cell therapy - Wikipedia

Induced stem cells – Wikipedia

By adminOctober 18, 2016Induced Pluripotent Stem Cells

Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. They are classified as either totipotent (iTC), pluripotent (iPSC) or progenitor (multipotentiMSC, also called an induced multipotent progenitor celliMPC) or unipotent(iUSC) according to their developmental potential and degree of dedifferentiation. Progenitors are obtained by so-called direct reprogramming or directed differentiation and are also called induced somatic stem cells.

Three techniques are widely recognized:[1]

In 1895 Thomas Morgan removed one of a frog's two blastomeres and found that amphibians are able to form whole embryos from the remaining part. This meant that the cells can change their differentiation pathway. In 1924 Spemann and Mangold demonstrated the key importance of cellcell inductions during animal development.[20] The reversible transformation of cells of one differentiated cell type to another is called metaplasia.[21] This transition can be a part of the normal maturation process, or caused by an inducement.

One example is the transformation of iris cells to lens cells in the process of maturation and transformation of retinal pigment epithelium cells into the neural retina during regeneration in adult newt eyes. This process allows the body to replace cells not suitable to new conditions with more suitable new cells. In Drosophila imaginal discs, cells have to choose from a limited number of standard discrete differentiation states. The fact that transdetermination (change of the path of differentiation) often occurs for a group of cells rather than single cells shows that it is induced rather than part of maturation.[22]

The researchers were able to identify the minimal conditions and factors that would be sufficient for starting the cascade of molecular and cellular processes to instruct pluripotent cells to organize the embryo. They showed that opposing gradients of bone morphogenetic protein (BMP) and Nodal, two transforming growth factor family members that act as morphogens, are sufficient to induce molecular and cellular mechanisms required to organize, in vivo or in vitro, uncommitted cells of the zebrafish blastula animal pole into a well-developed embryo.[23]

Some types of mature, specialized adult cells can naturally revert to stem cells. For example, "chief" cells express the stem cell marker Troy. While they normally produce digestive fluids for the stomach, they can revert into stem cells to make temporary repairs to stomach injuries, such as a cut or damage from infection. Moreover, they can make this transition even in the absence of noticeable injuries and are capable of replenishing entire gastric units, in essence serving as quiescent "reserve" stem cells.[24] Differentiated airway epithelial cells can revert into stable and functional stem cells in vivo.[25]

After injury, mature terminally differentiated kidney cells dedifferentiate into more primordial versions of themselves and then differentiate into the cell types needing replacement in the damaged tissue[26] Macrophages can self-renew by local proliferation of mature differentiated cells.[27][28] In newts, muscle tissue is regenerated from specialized muscle cells that dedifferentiate and forget the type of cell they had been. This capacity to regenerate does not decline with age and may be linked to their ability to make new stem cells from muscle cells on demand.[29]

A variety of nontumorigenic stem cells display the ability to generate multiple cell types. For instance, multilineage-differentiating stress-enduring (Muse) cells are stress-tolerant adult human stem cells that can self-renew. They form characteristic cell clusters in suspension culture that express a set of genes associated with pluripotency and can differentiate into endodermal, ectodermal and mesodermal cells both in vitro and in vivo.[30][31][32][33][34]

Other well-documented examples of transdifferentiation and their significance in development and regeneration were described in detail.[35][36]

Induced totipotent cells can be obtained by reprogramming somatic cells with somatic-cell nuclear transfer (SCNT). The process involves sucking out the nucleus of a somatic (body) cell and injecting it into an oocyte that has had its nucleus removed[3][5][37][38]

Using an approach based on the protocol outlined by Tachibana et al.,[3] hESCs can be generated by SCNT using dermal fibroblasts nuclei from both a middle-aged 35-year-old male and an elderly, 75-year-old male, suggesting that age-associated changes are not necessarily an impediment to SCNT-based nuclear reprogramming of human cells.[39] Such reprogramming of somatic cells to a pluripotent state holds huge potentials for regenerative medicine. Unfortunately, the cells generated by this technology, potentially are not completely protected from the immune system of the patient (donor of nuclei), because they have the same mitochondrial DNA, as a donor of oocytes, instead of the patients mitochondrial DNA. This reduces their value as a source for autologous stem cell transplantation therapy, as for the present, it is not clear whether it can induce an immune response of the patient upon treatment.

Induced androgenetic haploid embryonic stem cells can be used instead of sperm for cloning. These cells, synchronized in M phase and injected into the oocyte can produce viable offspring.[40]

These developments, together with data on the possibility of unlimited oocytes from mitotically active reproductive stem cells,[41] offer the possibility of industrial production of transgenic farm animals. Repeated recloning of viable mice through a SCNT method that includes a histone deacetylase inhibitor, trichostatin, added to the cell culture medium,[42] show that it may be possible to reclone animals indefinitely with no visible accumulation of reprogramming or genomic errors[43] However, research into technologies to develop sperm and egg cells from stem cells raises bioethical issues.[44]

Such technologies may also have far-reaching clinical applications for overcoming cytoplasmic defects in human oocytes.[3][45] For example, the technology could prevent inherited mitochondrial disease from passing to future generations. Mitochondrial genetic material is passed from mother to child. Mutations can cause diabetes, deafness, eye disorders, gastrointestinal disorders, heart disease, dementia and other neurological diseases. The nucleus from one human egg has been transferred to another, including its mitochondria, creating a cell that could be regarded as having two mothers. The eggs were then fertilised and the resulting embryonic stem cells carried the swapped mitochondrial DNA.[46] As evidence that the technique is safe author of this method points to the existence of the healthy monkeys that are now more than four years old and are the product of mitochondrial transplants across different genetic backgrounds.[47]

In late-generation telomerase-deficient (Terc/) mice, SCNT-mediated reprogramming mitigates telomere dysfunction and mitochondrial defects to a greater extent than iPSC-based reprogramming.[48]

Other cloning and totipotent transformation achievements have been described.[49]

Recently some researchers succeeded to get the totipotent cells without the aid of SCNT. Totipotent cells were obtained using the epigenetic factors such as oocyte germinal isoform of histone.[50] Reprogramming in vivo, by transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice, confers totipotency features. Intraperitoneal injection of such in vivo iPS cells generates embryo-like structures that express embryonic and extraembryonic (trophectodermal) markers.[51]

iPSc were first obtained in the form of transplantable teratocarcinoma induced by grafts taken from mouse embryos.[52] Teratocarcinoma formed from somatic cells.[53]Genetically mosaic mice were obtained from malignant teratocarcinoma cells, confirming the cells' pluripotency.[54][55][56] It turned out that teratocarcinoma cells are able to maintain a culture of pluripotent embryonic stem cell in an undifferentiated state, by supplying the culture medium with various factors.[57] In the 1980s, it became clear that transplanting pluripotent/embryonic stem cells into the body of adult mammals, usually leads to the formation of teratomas, which can then turn into a malignant tumor teratocarcinoma.[58] However, putting teratocarcinoma cells into the embryo at the blastocyst stage, caused them to become incorporated in the inner cell mass and often produced a normal chimeric (i.e. composed of cells from different organisms) animal.[59][60][61] This indicated that the cause of the teratoma is a dissonance - mutual miscommunication between young donor cells and surrounding adult cells (the recipient's so-called "niche").

In August 2006, Japanese researchers circumvented the need for an oocyte, as in SCNT. By reprograming mouse embryonic fibroblasts into pluripotent stem cells via the ectopic expression of four transcription factors, namely Oct4, Sox2, Klf4 and c-Myc, they proved that the overexpression of a small number of factors can push the cell to transition to a new stable state that is associated with changes in the activity of thousands of genes.[7]

Reprogramming mechanisms are thus linked, rather than independent and are centered on a small number of genes.[62] IPSC properties are very similar to ESCs.[63] iPSCs have been shown to support the development of all-iPSC mice using a tetraploid (4n) embryo,[64] the most stringent assay for developmental potential. However, some genetically normal iPSCs failed to produce all-iPSC mice because of aberrant epigenetic silencing of the imprinted Dlk1-Dio3 gene cluster.[18]

An important advantage of iPSC over ESC is that they can be derived from adult cells, rather than from embryos. Therefore, it became possible to obtain iPSC from adult and even elderly patients.[9][65][66]

Reprogramming somatic cells to iPSC leads to rejuvenation. It was found that reprogramming leads to telomere lengthening and subsequent shortening after their differentiation back into fibroblast-like derivatives.[67] Thus, reprogramming leads to the restoration of embryonic telomere length,[68] and hence increases the potential number of cell divisions otherwise limited by the Hayflick limit.[69]

However, because of the dissonance between rejuvenated cells and the surrounding niche of the recipient's older cells, the injection of his own iPSC usually leads to an immune response,[70] which can be used for medical purposes,[71] or the formation of tumors such as teratoma.[72] The reason has been hypothesized to be that some cells differentiated from ESC and iPSC in vivo continue to synthesize embryonic protein isoforms.[73] So, the immune system might detect and attack cells that are not cooperating properly.

A small molecule called MitoBloCK-6 can force the pluripotent stem cells to die by triggering apoptosis (via cytochrome c release across the mitochondrial outer membrane) in human pluripotent stem cells, but not in differentiated cells. Shortly after differentiation, daughter cells became resistant to death. When MitoBloCK-6 was introduced to differentiated cell lines, the cells remained healthy. The key to their survival, was hypothesized to be due to the changes undergone by pluripotent stem cell mitochondria in the process of cell differentiation. This ability of MitoBloCK-6 to separate the pluripotent and differentiated cell lines has the potential to reduce the risk of teratomas and other problems in regenerative medicine.[74]

In 2012 other small molecules (selective cytotoxic inhibitors of human pluripotent stem cellshPSCs) were identified that prevented human pluripotent stem cells from forming teratomas in mice. The most potent and selective compound of them (PluriSIn #1) inhibits stearoyl-coA desaturase (the key enzyme in oleic acid biosynthesis), which finally results in apoptosis. With the help of this molecule the undifferentiated cells can be selectively removed from culture.[75][76] An efficient strategy to selectively eliminate pluripotent cells with teratoma potential is targeting pluripotent stem cell-specific antiapoptotic factor(s) (i.e., survivin or Bcl10). A single treatment with chemical survivin inhibitors (e.g., quercetin or YM155) can induce selective and complete cell death of undifferentiated hPSCs and is claimed to be sufficient to prevent teratoma formation after transplantation.[77] However, it is unlikely that any kind of preliminary clearance,[78] is able to secure the replanting iPSC or ESC. After the selective removal of pluripotent cells, they re-emerge quickly by reverting differentiated cells into stem cells, which leads to tumors.[79] This may be due to the disorder of let-7 regulation of its target Nr6a1 (also known as Germ cell nuclear factor - GCNF), an embryonic transcriptional repressor of pluripotency genes that regulates gene expression in adult fibroblasts following micro-RNA miRNA loss.[80]

Teratoma formation by pluripotent stem cells may be caused by low activity of PTEN enzyme, reported to promote the survival of a small population (0,1-5% of total population) of highly tumorigenic, aggressive, teratoma-initiating embryonic-like carcinoma cells during differentiation. The survival of these teratoma-initiating cells is associated with failed repression of Nanog as well as a propensity for increased glucose and cholesterol metabolism.[81] These teratoma-initiating cells also expressed a lower ratio of p53/p21 when compared to non-tumorigenic cells.[82] In connection with the above safety problems, the use iPSC for cell therapy is still limited.[83] However, they can be used for a variety of other purposes - including the modeling of disease,[84] screening (selective selection) of drugs, toxicity testing of various drugs.[85]

It is interesting to note that the tissue grown from iPSCs, placed in the "chimeric" embryos in the early stages of mouse development, practically do not cause an immune response (after the embryos have grown into adult mice) and are suitable for autologous transplantation[86] At the same time, full reprogramming of adult cells in vivo within tissues by transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice results in teratomas emerging from multiple organs.[51] Furthermore, partial reprogramming of cells toward pluripotency in vivo in mice demonstrates that incomplete reprogramming entails epigenetic changes (failed repression of Polycomb targets and altered DNA methylation) in cells that drive cancer development.[87]

Determining the unique set of cellular factors that is needed to be manipulated for each cell conversion is a long and costly process that involved much trial and error. As a result, this first step of identifying the key set of cellular factors for cell conversion is the major obstacle researchers face in the field of cell reprogramming. An international team of researchers have developed an algorithm, called Mogrify(1), that can predict the optimal set of cellular factors required to convert one human cell type to another. When tested, Mogrify was able to accurately predict the set of cellular factors required for previously published cell conversions correctly. To further validate Mogrify's predictive ability, the team conducted two novel cell conversions in the laboratory using human cells and these were successful in both attempts solely using the predictions of Mogrify.[89][90][91] Mogrify has been made available online for other researchers and scientists.

By using solely small molecules, Deng Hongkui and colleagues demonstrated that endogenous "master genes" are enough for cell fate reprogramming. They induced a pluripotent state in adult cells from mice using seven small-molecule compounds.[17] The effectiveness of the method is quite high: it was able to convert 0.02% of the adult tissue cells into iPSCs, which is comparable to the gene insertion conversion rate. The authors note that the mice generated from CiPSCs were "100% viable and apparently healthy for up to 6 months". So, this chemical reprogramming strategy has potential use in generating functional desirable cell types for clinical applications.[92][93]

In 2015th year a robust chemical reprogramming system was established with a yield up to 1,000-fold greater than that of the previously reported protocol. So, chemical reprogramming became a promising approach to manipulate cell fates.[94]

The fact that human iPSCs capable of forming teratomas not only in humans but also in some animal body, in particular in mice or pigs, allowed to develop a method for differentiation of iPSCs in vivo. For this purpose, iPSCs with an agent for inducing differentiation into target cells are injected to genetically modified pig or mouse that has suppressed immune system activation on human cells. The formed teratoma is cut out and used for the isolation of the necessary differentiated human cells[95] by means of monoclonal antibody to tissue-specific markers on the surface of these cells. This method has been successfully used for the production of functional myeloid, erythroid and lymphoid human cells suitable for transplantation (yet only to mice).[96] Mice engrafted with human iPSC teratoma-derived hematopoietic cells produced human B and T cells capable of functional immune responses. These results offer hope that in vivo generation of patient customized cells is feasible, providing materials that could be useful for transplantation, human antibody generation and drug screening applications. Using MitoBloCK-6[74] and/or PluriSIn # 1 the differentiated progenitor cells can be further purified from teratoma forming pluripotent cells. The fact, that the differentiation takes place even in the teratoma niche, offers hope that the resulting cells are sufficiently stable to stimuli able to cause their transition back to the dedifferentiated (pluripotent) state and therefore safe. A similar in vivo differentiation system, yielding engraftable hematopoietic stem cells from mouse and human iPSCs in teratoma-bearing animals in combination with a maneuver to facilitate hematopoiesis, was described by Suzuki et al.[97] They noted that neither leukemia nor tumors were observed in recipients after intravenous injection of iPSC-derived hematopoietic stem cells into irradiated recipients. Moreover, this injection resulted in multilineage and long-term reconstitution of the hematolymphopoietic system in serial transfers. Such system provides a useful tool for practical application of iPSCs in the treatment of hematologic and immunologic diseases.[98]

For further development of this method animal in which is grown the human cell graft, for example mouse, must have so modified genome that all its cells express and have on its surface human SIRP.[99] To prevent rejection after transplantation to the patient of the allogenic organ or tissue, grown from the pluripotent stem cells in vivo in the animal, these cells should express two molecules: CTLA4-Ig, which disrupts T cell costimulatory pathways and PD-L1, which activates T cell inhibitory pathway.[100]

Embryonic stem cell – Wikipedia

By adminOctober 17, 2016Embryonic Stem Cells

Embryonic stem cells (ES cells) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage preimplantation embryo.[1][2] Human embryos reach the blastocyst stage 45 days post fertilization, at which time they consist of 50150 cells. Isolating the embryoblast or inner cell mass (ICM) results in destruction of the blastocyst, which raises ethical issues, including whether or not embryos at the pre-implantation stage should be considered to have the same moral or legal status as more developed human beings.[3][4]

Human ES cells measure approximately 14 m while mouse ES cells are closer to 8 m.[5]

Embryonic stem cells, derived from the blastocyst stage early mammalian embryos, are distinguished by their ability to differentiate into any cell type and by their ability to propagate. Embryonic stem cell's properties include having a normal karyotype, maintaining high telomerase activity, and exhibiting remarkable long-term proliferative potential.[6]

Embryonic stem cells of the inner cell mass are pluripotent, that is, they are able to differentiate to generate primitive ectoderm, which ultimately differentiates during gastrulation into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm. These include each of the more than 220 cell types in the adult body. Pluripotency distinguishes embryonic stem cells from adult stem cells found in adults; while embryonic stem cells can generate all cell types in the body, adult stem cells are multipotent and can produce only a limited number of cell types. If the pluripotent differentiation potential of embryonic stem cells could be harnessed in vitro, it might be a means of deriving cell or tissue types virtually to order. This would provide a radical new treatment approach to a wide variety of conditions where age, disease, or trauma has led to tissue damage or dysfunction.

Additionally, under defined conditions, embryonic stem cells are capable of propagating themselves indefinitely in an undifferentiated state and have the capacity when provided with the appropriate signals to differentiate, presumably via the formation of precursor cells, to almost all mature cell phenotypes.[7] This allows embryonic stem cells to be employed as useful tools for both research and regenerative medicine, because they can produce limitless numbers of themselves for continued research or clinical use.

Because of their plasticity and potentially unlimited capacity for self-renewal, embryonic stem cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. Diseases that could potentially be treated by pluripotent stem cells include a number of blood and immune-system related genetic diseases, cancers, and disorders; juvenile diabetes; Parkinson's disease; blindness and spinal cord injuries. Besides the ethical concerns of stem cell therapy (see stem cell controversy), there is a technical problem of graft-versus-host disease associated with allogeneic stem cell transplantation. However, these problems associated with histocompatibility may be solved using autologous donor adult stem cells, therapeutic cloning. Stem cell banks or more recently by reprogramming of somatic cells with defined factors (e.g. induced pluripotent stem cells). Embryonic stem cells provide hope that it will be possible to overcome the problems of donor tissue shortage and also, by making the cells immunocompatible with the recipient. Other potential uses of embryonic stem cells include investigation of early human development, study of genetic disease and as in vitro systems for toxicology testing.[6]

According to a 2002 article in PNAS, "Human embryonic stem cells have the potential to differentiate into various cell types, and, thus, may be useful as a source of cells for transplantation or tissue engineering."[8]

Current research focuses on differentiating ES into a variety of cell types for eventual use as cell replacement therapies (CRTs). Some of the cell types that have or are currently being developed include cardiomyocytes (CM), neurons, hepatocytes, bone marrow cells, islet cells and endothelial cells.[9] However, the derivation of such cell types from ESs is not without obstacles and hence current research is focused on overcoming these barriers. For example, studies are underway to differentiate ES in to tissue specific CMs and to eradicate their immature properties that distinguish them from adult CMs.[10]

Besides in the future becoming an important alternative to organ transplants, ES are also being used in field of toxicology and as cellular screens to uncover new chemical entities (NCEs) that can be developed as small molecule drugs. Studies have shown that cardiomyocytes derived from ES are validated in vitro models to test drug responses and predict toxicity profiles.[9] ES derived cardiomyocytes have been shown to respond to pharmacological stimuli and hence can be used to assess cardiotoxicity like Torsades de Pointes.[11]

ES-derived hepatocytes are also useful models that could be used in the preclinical stages of drug discovery. However, the development of hepatocytes from ES has proven to be challenging and this hinders the ability to test drug metabolism. Therefore, current research is focusing on establishing fully functional ES-derived hepatocytes with stable phase I and II enzyme activity.[12]

Researchers have also differentiated ES into dopamine-producing cells with the hope that these neurons could be used in the treatment of Parkinsons disease.[13][14] Recently, the development of ESC after Somatic Cell Nuclear Transfer (SCNT) of Olfactory ensheathing cells (OEC's) to a healthy Oocyte has been recommended for Neuro-degenerative diseases.[15] ESs have also been differentiated to natural killer (NK) cells and bone tissue.[16] Studies involving ES are also underway to provide an alternative treatment for diabetes. For example, DAmour et al. were able to differentiate ES into insulin producing cells[17] and researchers at Harvard University were able to produce large quantities of pancreatic beta cells from ES.[18]

Several new studies have started to address this issue. This has been done either by genetically manipulating the cells, or more recently by deriving diseased cell lines identified by prenatal genetic diagnosis (PGD). This approach may very well prove invaluable at studying disorders such as Fragile-X syndrome, Cystic fibrosis, and other genetic maladies that have no reliable model system.

Yury Verlinsky, a Russian-American medical researcher who specialized in embryo and cellular genetics (genetic cytology), developed prenatal diagnosis testing methods to determine genetic and chromosomal disorders a month and a half earlier than standard amniocentesis. The techniques are now used by many pregnant women and prospective parents, especially those couples with a history of genetic abnormalities or where the woman is over the age of 35, when the risk of genetically related disorders is higher. In addition, by allowing parents to select an embryo without genetic disorders, they have the potential of saving the lives of siblings that already had similar disorders and diseases using cells from the disease free offspring.[19]

Scientists have discovered a new technique for deriving human embryonic stem cell (ESC). Normal ESC lines from different sources of embryonic material including morula and whole blastocysts have been established. These findings allows researchers to construct ESC lines from embryos that acquire different genetic abnormalities; therefore, allowing for recognition of mechanisms in the molecular level that are possibly blocked that could impede the disease progression. The ESC lines originating from embryos with genetic and chromosomal abnormalities provide the data necessary to understand the pathways of genetic defects.[20]

A donor patient acquires one defective gene copy and one normal, and only one of these two copies is used for reproduction. By selecting egg cell derived from embryonic stem cells that have two normal copies, researchers can find variety of treatments for various diseases. To test this theory Dr. McLaughlin and several of his colleagues looked at whether parthenogenetic embryonic stem cells can be used in a mouse model that has thalassemia intermedia. This disease is described as an inherited blood disorder in which there is a lack of hemoglobin leading to anemia. The mouse model used, had one defective gene copy. Embryonic stem cells from an unfertilized egg of the diseased mice were gathered and those stem cells that contained only healthy hemoglobin genes were identified. The healthy embryonic stem cell lines were then converted into cells transplanted into the carrier mice. After five weeks, the test results from the transplant illustrated that these carrier mice now had a normal blood cell count and hemoglobin levels.[21]

Differentiated somatic cells and ES cells use different strategies for dealing with DNA damage. For instance, human foreskin fibroblasts, one type of somatic cell, use non-homologous end joining (NHEJ), an error prone DNA repair process, as the primary pathway for repairing double-strand breaks (DSBs) during all cell cycle stages.[22] Because of its error-prone nature, NHEJ tends to produce mutations in a cells clonal descendants.

ES cells use a different strategy to deal with DSBs.[23] Because ES cells give rise to all of the cell types of an organism including the cells of the germ line, mutations arising in ES cells due to faulty DNA repair are a more serious problem than in differentiated somatic cells. Consequently, robust mechanisms are needed in ES cells to repair DNA damages accurately, and if repair fails, to remove those cells with un-repaired DNA damages. Thus, mouse ES cells predominantly use high fidelity homologous recombinational repair (HRR) to repair DSBs.[23] This type of repair depends on the interaction of the two sister chromosomes formed during S phase and present together during the G2 phase of the cell cycle. HRR can accurately repair DSBs in one sister chromosome by using intact information from the other sister chromosome. Cells in the G1 phase of the cell cycle (i.e. after metaphase/cell division but prior the next round of replication) have only one copy of each chromosome (i.e. sister chromosomes arent present). Mouse ES cells lack a G1 checkpoint and do not undergo cell cycle arrest upon acquiring DNA damage.[24] Rather they undergo programmed cell death (apoptosis) in response to DNA damage.[25] Apoptosis can be used as a fail-safe strategy to remove cells with un-repaired DNA damages in order to avoid mutation and progression to cancer.[26] Consistent with this strategy, mouse ES stem cells have a mutation frequency about 100-fold lower than that of isogenic mouse somatic cells.[27]

The major concern with the possible transplantation of ESC into patients as therapies is their ability to form tumors including teratoma.[28] Safety issues prompted the FDA to place a hold on the first ESC clinical trial (see below), however no tumors were observed.

The main strategy to enhance the safety of ESC for potential clinical use is to differentiate the ESC into specific cell types (e.g. neurons, muscle, liver cells) that have reduced or eliminated ability to cause tumors. Following differentiation, the cells are subjected to sorting by flow cytometry for further purification. ESC are predicted to be inherently safer than IPS cells because they are not genetically modified with genes such as c-Myc that are linked to cancer. Nonetheless, ESC express very high levels of the iPS inducing genes and these genes including Myc are essential for ESC self-renewal and pluripotency,[29] and potential strategies to improve safety by eliminating Myc expression are unlikely to preserve the cells' "stemness".

In 1964, Lewis Kleinsmith and G. Barry Pierce Jr. isolated a single type of cell from a teratocarcinoma, a tumor now known to be derived from a germ cell.[30] These cells isolated from the teratocarcinoma replicated and grew in cell culture as a stem cell and are now known as embryonal carcinoma (EC) cells.[31] Although similarities in morphology and differentiating potential (pluripotency) led to the use of EC cells as the in vitro model for early mouse development,[32] EC cells harbor genetic mutations and often abnormal karyotypes that accumulated during the development of the teratocarcinoma. These genetic aberrations further emphasized the need to be able to culture pluripotent cells directly from the inner cell mass.

In 1981, embryonic stem cells (ES cells) were independently first derived from mouse embryos by two groups. Martin Evans and Matthew Kaufman from the Department of Genetics, University of Cambridge published first in July, revealing a new technique for culturing the mouse embryos in the uterus to allow for an increase in cell number, allowing for the derivation of ES cells from these embryos.[33]Gail R. Martin, from the Department of Anatomy, University of California, San Francisco, published her paper in December and coined the term Embryonic Stem Cell.[34] She showed that embryos could be cultured in vitro and that ES cells could be derived from these embryos. In 1998, a breakthrough occurred when researchers, led by James Thomson at the University of Wisconsin-Madison, first developed a technique to isolate and grow human embryonic stem cells in cell culture.[35]

On January 23, 2009, Phase I clinical trials for transplantation of oligodendrocytes (a cell type of the brain and spinal cord) derived from human ES cells into spinal cord-injured individuals received approval from the U.S. Food and Drug Administration (FDA), marking it the world's first human ES cell human trial.[36] The study leading to this scientific advancement was conducted by Hans Keirstead and colleagues at the University of California, Irvine and supported by Geron Corporation of Menlo Park, CA, founded by Michael D. West, PhD. A previous experiment had shown an improvement in locomotor recovery in spinal cord-injured rats after a 7-day delayed transplantation of human ES cells that had been pushed into an oligodendrocytic lineage.[37] The phase I clinical study was designed to enroll about eight to ten paraplegics who have had their injuries no longer than two weeks before the trial begins, since the cells must be injected before scar tissue is able to form. The researchers emphasized that the injections were not expected to fully cure the patients and restore all mobility. Based on the results of the rodent trials, researchers speculated that restoration of myelin sheathes and an increase in mobility might occur. This first trial was primarily designed to test the safety of these procedures and if everything went well, it was hoped that it would lead to future studies that involve people with more severe disabilities.[38] The trial was put on hold in August 2009 due to FDA concerns regarding a small number of microscopic cysts found in several treated rat models but the hold was lifted on July 30, 2010.[39]

In October 2010 researchers enrolled and administered ESTs to the first patient at Shepherd Center in Atlanta.[40] The makers of the stem cell therapy, Geron Corporation, estimated that it would take several months for the stem cells to replicate and for the GRNOPC1 therapy to be evaluated for success or failure.

In November 2011 Geron announced it was halting the trial and dropping out of stem cell research for financial reasons, but would continue to monitor existing patients, and was attempting to find a partner that could continue their research.[41] In 2013 BioTime (NYSEMKT:BTX), led by CEO Dr. Michael D. West, acquired all of Geron's stem cell assets, with the stated intention of restarting Geron's embryonic stem cell-based clinical trial for spinal cord injury research.[42]

In vitro fertilization generates multiple embryos. The surplus of embryos is not clinically used or is unsuitable for implantation into the patient, and therefore may be donated by the donor with consent. Human embryonic stem cells can be derived from these donated embryos or additionally they can also be extracted from cloned embryos using a cell from a patient and a donated egg.[43] The inner cell mass (cells of interest), from the blastocyst stage of the embryo, is separated from the trophectoderm, the cells that would differentiate into extra-embryonic tissue. Immunosurgery, the process in which antibodies are bound to the trophectoderm and removed by another solution, and mechanical dissection are performed to achieve separation. The resulting inner cell mass cells are plated onto cells that will supply support. The inner cell mass cells attach and expand further to form a human embryonic cell line, which are undifferentiated. These cells are fed daily and are enzymatically or mechanically separated every four to seven days. For differentiation to occur, the human embryonic stem cell line is removed from the supporting cells to form embryoid bodies, is co-cultured with a serum containing necessary signals, or is grafted in a three-dimensional scaffold to result.[44]

Embryonic stem cells are derived from the inner cell mass of the early embryo, which are harvested from the donor mother animal. Martin Evans and Matthew Kaufman reported a technique that delays embryo implantation, allowing the inner cell mass to increase. This process includes removing the donor mother's ovaries and dosing her with progesterone, changing the hormone environment, which causes the embryos to remain free in the uterus. After 46 days of this intrauterine culture, the embryos are harvested and grown in in vitro culture until the inner cell mass forms egg cylinder-like structures, which are dissociated into single cells, and plated on fibroblasts treated with mitomycin-c (to prevent fibroblast mitosis). Clonal cell lines are created by growing up a single cell. Evans and Kaufman showed that the cells grown out from these cultures could form teratomas and embryoid bodies, and differentiate in vitro, all of which indicating that the cells are pluripotent.[33]

Gail Martin derived and cultured her ES cells differently. She removed the embryos from the donor mother at approximately 76 hours after copulation and cultured them overnight in a medium containing serum. The following day, she removed the inner cell mass from the late blastocyst using microsurgery. The extracted inner cell mass was cultured on fibroblasts treated with mitomycin-c in a medium containing serum and conditioned by ES cells. After approximately one week, colonies of cells grew out. These cells grew in culture and demonstrated pluripotent characteristics, as demonstrated by the ability to form teratomas, differentiate in vitro, and form embryoid bodies. Martin referred to these cells as ES cells.[34]

It is now known that the feeder cells provide leukemia inhibitory factor (LIF) and serum provides bone morphogenetic proteins (BMPs) that are necessary to prevent ES cells from differentiating.[45][46] These factors are extremely important for the efficiency of deriving ES cells. Furthermore, it has been demonstrated that different mouse strains have different efficiencies for isolating ES cells.[47] Current uses for mouse ES cells include the generation of transgenic mice, including knockout mice. For human treatment, there is a need for patient specific pluripotent cells. Generation of human ES cells is more difficult and faces ethical issues. So, in addition to human ES cell research, many groups are focused on the generation of induced pluripotent stem cells (iPS cells).[48]

On August 23, 2006, the online edition of Nature scientific journal published a letter by Dr. Robert Lanza (medical director of Advanced Cell Technology in Worcester, MA) stating that his team had found a way to extract embryonic stem cells without destroying the actual embryo.[49] This technical achievement would potentially enable scientists to work with new lines of embryonic stem cells derived using public funding in the USA, where federal funding was at the time limited to research using embryonic stem cell lines derived prior to August 2001. In March, 2009, the limitation was lifted.[50]

In 2007 it was shown that pluripotent stem cells highly similar to embryonic stem cells can be generated by the delivery of three genes (Oct4, Sox2, and Klf4) to differentiated cells.[51] The delivery of these genes "reprograms" differentiated cells into pluripotent stem cells, allowing for the generation of pluripotent stem cells without the embryo. Because ethical concerns regarding embryonic stem cells typically are about their derivation from terminated embryos, it is believed that reprogramming to these "induced pluripotent stem cells" (iPS cells) may be less controversial. Both human and mouse cells can be reprogrammed by this methodology, generating both human pluripotent stem cells and mouse pluripotent stem cells without an embryo.[52]

This may enable the generation of patient specific ES cell lines that could potentially be used for cell replacement therapies. In addition, this will allow the generation of ES cell lines from patients with a variety of genetic diseases and will provide invaluable models to study those diseases.

However, as a first indication that the induced pluripotent stem cell (iPS) cell technology can in rapid succession lead to new cures, it was used by a research team headed by Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, to cure mice of sickle cell anemia, as reported by Science journal's online edition on December 6, 2007.[53][54]

On January 16, 2008, a California-based company, Stemagen, announced that they had created the first mature cloned human embryos from single skin cells taken from adults. These embryos can be harvested for patient matching embryonic stem cells.[55]

The online edition of Nature Medicine published a study on January 24, 2005, which stated that the human embryonic stem cells available for federally funded research are contaminated with non-human molecules from the culture medium used to grow the cells.[56] It is a common technique to use mouse cells and other animal cells to maintain the pluripotency of actively dividing stem cells. The problem was discovered when non-human sialic acid in the growth medium was found to compromise the potential uses of the embryonic stem cells in humans, according to scientists at the University of California, San Diego.[57]

However, a study published in the online edition of Lancet Medical Journal on March 8, 2005 detailed information about a new stem cell line that was derived from human embryos under completely cell- and serum-free conditions. After more than 6 months of undifferentiated proliferation, these cells demonstrated the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. These properties were also successfully maintained (for more than 30 passages) with the established stem cell lines.[58]

Visit link:
Embryonic stem cell - Wikipedia

Home | The EMBO Journal

By adminOctober 16, 2016Stem Cell Medical Center

Open Access

Article

The Arabidopsis CERK1associated kinase PBL27 connects chitin perception to MAPK activation

These authors contributed equally to this work as first authors

These authors contributed equally to this work as third authors

Chitin receptor CERK1 transmits immune signals to the intracellular MAPK cascade in plants. This occurs via phosphorylation of MAPKKK5 by the CERK1associated kinase PBL27, providing a missing link between pathogen perception and signaling output.

CERK1associated kinase PBL27 interacts with MAPKKK5 at the plasma membrane.

Chitin perception induces disassociation of PBL27 and MAPKKK5.

PBL27 functions as a MAPKKK kinase.

Phosphorylation of MAPKKK5 by PBL27 is enhanced upon phosphorylation of PBL27 by CERK1.

Phosphorylation of MAPKKK5 by PBL27 is required for chitininduced MAPK activation in planta.

Kenta Yamada, Koji Yamaguchi, Tomomi Shirakawa, Hirofumi Nakagami, Akira Mine, Kazuya Ishikawa, Masayuki Fujiwara, Mari Narusaka, Yoshihiro Narusaka, Kazuya Ichimura, Yuka Kobayashi, Hidenori Matsui, Yuko Nomura, Mika Nomoto, Yasuomi Tada, Yoichiro Fukao, Tamo Fukamizo, Kenichi Tsuda, Ken Shirasu, Naoto Shibuya, Tsutomu Kawasaki

Here is the original post:
Home | The EMBO Journal

Home | EMBO Reports

By adminOctober 16, 2016Stem Cell Clinic

You have accessRestricted access

Article

The membrane scaffold SLP2 anchors a proteolytic hub in mitochondria containing PARL and the iAAA protease YME1L

These authors contributed equally to this work

The membrane scaffold SLP2 anchors a large protease complex containing the rhomboid protease PARL and the iAAA protease YME1L in the inner membrane of mitochondria, termed the SPY complex. Assembly into the SPY complex modulates PARL activity toward its substrate proteins PINK1 and PGAM5.

SLP2 assembles with PARL and YME1L into the SPY complex in the mitochondrial inner membrane.

Assembly into SPY complexes modulates PARLmediated processing of PINK1 and PGAM5.

SLP2 restricts OMA1mediated processing of the OPA1.

Timothy Wai, Shotaro Saita, Hendrik Nolte, Sebastian Mller, Tim Knig, Ricarda RichterDennerlein, HansGeorg Sprenger, Joaquin Madrenas, Mareike Mhlmeister, Ulrich Brandt, Marcus Krger, Thomas Langer

See the article here:
Home | EMBO Reports

Worlds Leading Immunology Congress | Conferenceseries

By adminOctober 16, 2016Uncategorized

Accreditation Statement

This activity (World Immunology Summit 2016) has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of PeerPoint Medical Education Institute and Conference Series, LLC. PeerPoint Medical Education Institute is accredited by the ACCME to provide continuing medical education for physicians.

Designation Statement

PeerPoint Medical Education Institute designates the live format for this educational activity for AMA PRA Category 1 Credits. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Conference series invites participants from all over the world to attend "6th International Conference and Exhibition on Immunology" October 24-26, 2016 Chicago, USA includes prompt keynote presentations, Oral talks, Poster presentations and Exhibitions.

Presenters can availupto 20 CME credits..

The annual International Conference on Immunology offer a unique platform for academia, Societies and Industries interested in immunology and Biomedical sciences to share the latest trends and important issues in the field. Immunology Summit-2016 brings together the Global leaders in Immunology and relevant fields to present their research at this exclusive scientific program. The Immunology Conference hosting presentations from editors of prominent refereed journals, renowned and active investigators and decision makers in the field of Immunology. Immunology Summit 2016 Organizing Committee also intended to encourage Young investigators at every career stage to submit abstracts reporting their latest scientific findings in oral and poster sessions.

Track 1:ClinicalImmunology: Current & Future Research

Immunology is the study of the immune system. The immune system is how all animals, including humans, protect themselves against diseases. The study of diseases caused by disorders of the immune system is clinical immunology. The disorders of the immune system fall into two broad categories:

Immunodeficiency, in this immune system fails to provide an adequate response.

Autoimmunity, in this immune system attacks its own host's body.

Related:Immunology Conferences|Immunologists Meetings|Conference Series LLC

2nd International Conference on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA;5th European Immunology Conferences, July 21-23, 2016 Berlin, Germany; 7th International Conference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands; 2nd international conference on innate immunity, July 21-22, 2016, Germany; International Conference on Autoimmunity, October 13-14, 2016 Manchester, UK; Immunology 2016, American Association of Immunologists, Annual MeetingMay 13-17, Los Angeles, USA;USA Immunology Conferences;InternationalConference onMucosalImmunology, July 28-29, 2016, Australia;International Congress of Immunology

Track 2:Cancer and Tumor Immunobiology

The immune system is the bodys first line of defence against most diseases and unnatural invaders.Cancer Immunobiologyis a branch ofimmunologyand it studies interactions between theimmune systemandcancer cells. These cancer cells, through subtle alterations, become immortal malignant cells but are often not changed enough to elicit an immune reaction.Understanding how the immune system worksor does not workagainst cancer is a primary focus of Cancer Immunology investigators. Certain cells of the immune system, including natural killer cells, dendritic cells (DCs) and effector T cells, are capable of driving potent anti-tumour responses.

Tumor Immunobiology

The immune system can promote the elimination of tumours, but often immune responses are modulated or suppressed by the tumour microenvironment. The Tumour microenvironment is an important aspect of cancer biology that contributes to tumour initiation, tumour progression and responses to therapy. Cells and molecules of the immune system are a fundamental component of the tumour microenvironment. Importantly, therapeutic strategies can harness the immune system to specifically target tumour cells and this is particularly appealing owing to the possibility of inducing tumour-specific immunological memory, which might cause long-lasting regression and prevent relapse in cancer patients. The composition and characteristics of the tumour micro environment vary widely and are important in determining the anti-tumour immune response. Tumour cells often induce an immunosuppressive microenvironment, which favours the development of immuno suppressive populations of immune cells, such as myeloid-derived suppressor cells and regulatory T cells.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

2nd International Conference and Exhibition on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; International Conference on Tumor Immunology and Immunotherapy, July 28-30, 2016 Melbourne, Australia; International Conference on Cancer Immunology and Immunotherapy, July 28-30, 2016 Melbourne, Australia, 2nd international congress on Neuroimmunology & therapeutics, Dec 01-03, 2016, USA; 2nd international conference on innate immunity, July 21-22, 2016, Germany;Immunology events;9th EuropeanMucosal ImmunologyMeetings, October 9 - 12 October, Scotland; international congress on immunology, august 21-26, 2016, Australia; 4th European Immunology events September 6-9, 2015, Austria

Track 3:Inflammation and Therapies

Inflammation is the body's attempt at self-protection; the aim being to remove harmful stimuli, including damaged cells, irritants, or pathogens - and begin the healing process. In Inflammation the body's whiteblood cellsand substances they produce protect us from infection with foreign organisms, such as bacteria and viruses. However, in some diseases, likearthritis, the body's defense system, the immune system triggers an inflammatory response when there are no foreign invaders to fight off. In these diseases, called autoimmune diseases, the body's normally protective immune system causes damage to its own tissues. The body responds as if normal tissues are infected or somehow abnormal. Inflammation involves immune cells, blood vessels, and molecular mediators. The purpose of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and to initiate tissue repair. signs of acute inflammation are pain, heat, redness, swelling, and loss of function

Therapies

Inflammation Therapy is a treatment for chronic disease involving a combination of lifestyle factors and medications designed to enable the immune system to fight the disease. Techniques used include heat therapy, cold therapy, electrical stimulation, traction, massage, and acupuncture. Heat increases blood flow and makes connective tissue more flexible. It temporarily decreases joint stiffness, pain, and muscle spasms. Heat also helps reduce inflammation and the buildup of fluid in tissues (edema). Heat therapy is used to treat inflammation (including various forms of arthritis), muscle spasm, and injuries such as sprains and strains. Cold therapy Applying cold may help numb tissues and relieve muscle spasms, pain due to injuries, and low back pain or inflammation that has recently developed. Cold may be applied using an ice bag, a cold pack, or fluids (such as ethyl chloride) that cool by evaporation. The therapist limits the time and amount of cold exposure to avoid damaging tissues and reducing body temperature (causing hypothermia). Cold is not applied to tissues with a reduced blood supply (for example, when the arteries are narrowed by peripheral arterial disease).

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

7th International Conference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands ; 5th European Immunology Conferences, July 21-23, 2016 Berlin, Germany; 2nd International Conference on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; International Conference on Tumor Immunology and Immunotherapy, July 28-30, 2016 Melbourne, Australia; International Conference on Cancer Immunology and Immunotherapy, July 28-30, 2016 Melbourne, Australia; InternationalcongressonImmunology, August 21-26, 2016, Australia; 18th International Conference on Inflammation, Amsterdam, Netherlands, May 12 - 13, 2016; 14th Cytokines & Inflammation Conference 2526 January 2016 San Diego, United States;

Track 4:Molecular and Structural Immunology

Molecular Immunology

Molecular immunology deals with immune responses at cellular and molecular level. Molecular immunology has been evolved for better understanding of the sub-cellular immune responses for prevention and treatment of immune related disorders and immune deficient diseases. Journal of molecular immunology focuses on the invitro and invivo immunological responses of the host. Molecular Immunology focuses on the areas such as immunological disorders, invitro and invivo immunological host responses, humoral responses, immunotherapies for treatment of cancer, treatment of autoimmune diseases such as Hashimotos disease, myasthenia gravis, rheumatoid arthritis and systemic lupus erythematosus. Treatment of Immune deficiencies such as hypersensitivities, chronic granulomatous disease, diagnostic immunology research aspects, allografts, etc..

Structural Immunology

Host immune system is an important and sophisticated system, maintaining the balance of host response to "foreign" antigens and ignorance to the normal-self. To fulfill this achievement the system manipulates a cell-cell interaction through appropriate interactions between cell-surface receptors and cell-surface ligands, or cell-secreted soluble effector molecules to their ligands/receptors/counter-receptors on the cell surface, triggering further downstream signaling for response effects. T cells and NK cells are important components of the immune system for defending the infections and malignancies and maintaining the proper response against over-reaction to the host. Receptors on the surface of T cells and NK cells include a number of important protein molecules, for example, T cell receptor (TCR), co-receptor CD8 or CD4, co-stimulator CD28, CTLA4, KIR, CD94/NKG2, LILR (ILT/LIR/CD85), Ly49, and so forth.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

2nd International Conference and Exhibition on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; 7th International Conference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands; 2nd international conference on innate immunity, July 21-22, 2016, Germany; International Conference on Autoimmunity, October 13-14, 2016 Manchester, UK; Immunology 2016, American Association of Immunologists, Annual MeetingMay 13-17, Los Angeles, USA;9th EuropeanMucosal ImmunologyMeetings, October 9 - 12 October, Scotland;Immunology events;International Congress of Immunology

Track 5:Transplantation Immunology

Transplantation is an act of transferring cells, tissues, or organ from one site to other. Graft is implanted cell, tissue or organ. Development of the field of organ and tissue transplantation has accelerated remarkably since the human major histocompatibility complex (mhc) was discovered in 1967. Matching of donor and recipient for mhc antigens has been shown to have a significant positive effect on graft acceptance. The roles of the different components of the immune system involved in the tolerance or rejection of grafts and in graft-versus-host disease have been clarified. These components include: antibodies, antigen presenting cells, helper and cytotoxic t cell subsets, immune cell surface molecules, signaling mechanisms and cytokines that they release. The development of pharmacologic and biological agents that interfere with the alloimmune response and graft rejection has had a crucial role in the success of organ transplantation. Combinations of these agents work synergistically, leading to lower doses of immunosuppressive drugs and reduced toxicity. Significant numbers of successful solid organ transplants include those of the kidneys, liver, heart and lung.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

2ndInternationalCongress onNeuroimmunology&Therapeutics, Dec 01-03, 2016, USA; 7th International Conference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands ; 2nd International Conference on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA;USA Immunology Conferences;International Conference on Tumor Immunology and Immunotherapy, July 28-30, 2016 Melbourne, Australia; International Conference on Cancer Immunology and Immunotherapy, July 28-30, 2016 Melbourne, Australia; British society for Immunology Annual Immunology Congress, 6-9 Dec, 2016, Liverpool, UK; InternationalConference onMucosalImmunology, July 28-29, 2016, Australia; Immunology events

Track 6:Infectious Diseases, Emerging and Reemerging diseases: Confronting Future Outbreaks

Infectious diseasesare disorders caused by organisms such as bacteria, viruses,fungior parasites. Many organisms live in and on our bodies. They're normally harmless or even helpful, but under certain conditions, some organisms may causedisease.Someinfectious diseasescan be passed from person to person. Many infectious diseases, such asmeaslesand chickenpox, can be prevented by vaccines. Frequent and thorough hand-washing also helps protect you from infectious diseases.

There are four main kinds of germs:

Bacteria - one-celled germs that multiply quickly and may release chemicals which can make you sick

Viruses- capsules that contain genetic material, and use your own cells to multiply

Fungi - primitive plants, like mushrooms or mildew

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

InternationalConference on Pediatric Care and Pediatric Infectious Disease, August 24-25, 2016 Philadelphia, Pennsylvania, USA; 4th InternationalCongress on Bacteriology and Infectious Diseases, May 16-18, 2016 San Antonio, Texas, USA; 2ndWorld Congress on Infectious DiseasesAugust 24 - 26, 2016 Philadelphia, Pennsylvania, USA; WorldCongress on Infection Prevention and Control, November 28-29, 2016 Valencia, Spain; Internationalconference on Emerging Infectious Diseases, Aug 24-26, Atlanta, Georgia;Immunology 2016, The 25th Annual CanadianConference on HIV/AIDSResearch Winnipeg, Manitoba, Canada , May 12, 2016 - May 15, 2016;Infectious DiseasesScandinavia-Russia Cruise 1626 June 2016, Copenhagen, Denmark; Immunology 2016, American Association of Immunologists, Annual Meeting May 13-17, Los Angeles, USA, 7th InternationalConference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands

Track 7:Autoimmune Diseases

An autoimmune disease develops when your immune system, which defends your body against disease, decides your healthy cells are foreign. As a result, your immune system attacks healthy cells. An autoimmune disorder may result in the destruction of body tissue, abnormal growth of an organ, Changes in organ function. Depending on the type, an autoimmune disease can affect one or many different types of body tissue. Areas often affected by autoimmune disorders include Blood vessels, Connective tissues, Endocrineglands such as the thyroid or pancreas, Joints Muscles, Red blood cells, Skin It can also cause abnormal organ growth and changes in organ function. There are as many as 80 types of autoimmune diseases. Many of them have similar symptoms, which makes them very difficult to diagnose. Its also possible to have more than one at the same time. Common autoimmune disorders include Addison's disease, Dermatomyositis, Graves' disease, Hashimoto's thyroiditis, Multiple sclerosis, Myasthenia gravis, Pernicious anemia, Reactive arthritis. Autoimmune diseases usually fluctuate between periods of remission (little or no symptoms) and flare-ups (worsening symptoms). Currently, treatment for autoimmune diseases focuses on relieving symptoms because there is no curative therapy.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

International Conference on Autoimmunity, October 13-14, 2016 Manchester, UK; 2nd international conference on innate immunity, July 21-22, 2016, Germany; 2nd International Conference andExhibition on Antibodiesand Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA;Immunology events; 5th European Immunology Conferences, July 21-23, 2016 Berlin, Germany; 7th International Conference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands; 2nd Conference on Rheumatic and Autoimmune Diseases, June 1 to 3, 2016 Nanjing, China; 18th International Autoimmune Diseases Meetings, Paris, France, September 26 - 27, 2016; British society for Immunology Annual Immunology Congress, 6-9 Dec, 2016, Liverpool, UK;International Congress of Immunology

Track 8:Viral Immunology: Emerging and Re-emerging Diseases

Immunology is the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and disease; malfunctions of the immune system in immunological disorders (autoimmune diseases, hypersensitivities, immune deficiency, transplant rejection); the physical, chemical and physiological characteristics of the components of the immune system in vitro, in situ, and in vivo.

Viruses are strongly immunogenic and induces 2 types of immune responses; humoral and cellular. The repertoire of specificities of T and B cells are formed by rearrangements and somatic mutations. T and B cells do not generally recognize the same epitopes present on the same virus. B cells see the free unaltered proteins in their native 3-D conformation whereas T cells usually see the Ag in a denatured form in conjunction with MHC molecules. The characteristics of the immune reaction to the same virus may differ in different individuals depending on their genetic constitutions.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

6thInternational Conference andExhibition onImmunology,Oct 24-26, 2016, USA;InternationalConference onAutoimmunity, Oct 24-26, 2016, UK;5thEuropeanImmunologyConference, July 21-23, 2016, Germany; InternationalConference onCancer ImmunologyandImmunotherapy, July 28-30, 2016, Australia;International Conference onMucosal Immunology, July 28-29, 2016, Australia; 2nd InternationalConference on Antibodiesand Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; InternationalConference on Tumor Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia; InternationalConference on Cancer Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia

Track 9:Pediatric Immunology

A child suffering from allergies or other problems with his immune system is referred as pediatric immunology. Childs immune system fights against infections. If the child has allergies, their immune system wrongly reacts to things that are usually harmless. Pet dander, pollen, dust, mold spores, insect stings, food, and medications are examples of such things. This reaction may cause their body to respond with health problems such as asthma, hay fever, hives, eczema (a rash), or a very severe and unusual reaction calledanaphylaxis. Sometimes, if your childs immune system is not working right, he may suffer from frequent, severe, and/or uncommon infections. Examples of such infections are sinusitis (inflammation of one or more of the sinuses), pneumonia (infection of the lung), thrush (a fungus infection in the mouth), and abscesses (collections of pus surrounded by inflamed tissue) that keep coming back.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

International Conference on Pediatric Care and Pediatric Infectious Disease, August 24-25, 2016 Philadelphia, Pennsylvania, USA; 7th International Conference on Pediatric Nursing and Healthcare, July 11-12, 2016 Cologne, Germany; International Congress on Pediatrics, 02-05 Jun 2016, Copenhagen, Denmark; 7th InternationalConference on Allergy, Asthma and Clinical Immunology, September 14;-15, 2016 Amsterdam, Netherlands; 2nd international conference on innate immunity, July 21-22, 2016, Germany; World Summit on Pediatric , 23 - 26 Jun 2016, Porto, Portugal; International Conference on Pediatric Nursing and Healthcare, Jul 11 - 13 2016, Cologne, Germany; Immunology 2016, American Association of Immunologists, Annual Meeting May 13-17, Los Angeles, USA; Immunology events;USA Immunology Conferences

Track 10:Immunotherapy & Cancer Immunotherapy: From Basic Biology to Translational Research

Immunotherapy is treatment that uses certain parts of a persons immune system to fight diseases such as cancer. This can be done in a couple of ways:

Stimulating your own immune system to work harder or smarter to attack cancer cells Giving you immune system components, such as man-made immune system proteins

Some types of immunotherapy are also sometimes called biologic therapy or biotherapy. In the last few decades immunotherapy has become an important part of treating some types of cancer. Newer types of immune treatments are now being studied, and theyll impact how we treat cancer in the future. Immunotherapy includes treatments that work in different ways. Some boost the bodys immune system in a very general way. Others help train the immune system to attack cancer cells specifically.

Cancer immunotherapy is the use of the immune system to treat cancer. The main types of immunotherapy now being used to treat cancer include:

Monoclonal antibodies: these are man-made versions of immune system proteins. Antibodies can be very useful in treating cancer because they can be designed to attack a very specific part of a cancer cell.

Immune checkpoint inhibitors: these drugs basically take the brakes off the immune system, which helps it recognize and attack cancer cells.

Cancer vaccines: vaccines are substances put into the body to start an immune response against certain diseases. We usually think of them as being given to healthy people to help prevent infections. But some vaccines can help prevent or treat cancer.

Other, non-specific immunotherapies: these treatments boost the immune system in a general way, but this can still help the immune system attack cancer cells.

Immunotherapy drugs are now used to treat many different types of cancer. For more information about immunotherapy as a treatment for a specific cancer, please see our information on that type of cancer.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

2nd International Conference and Exhibition on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; InternationalConference on Tumor Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia; InternationalConference on Cancer Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia, 2nd internationalCongress on Neuroimmunology& therapeutics, Dec 01-03, 2016, USA;International Congress of Immunology;2nd international conference on innate immunity, July 21-22, 2016, Germany;5th European Immunology Conferences, July 21-23, 2016 Berlin, Germany; 9th European Mucosal Immunology meetings, October 9 - 12 October, Scotland; international congress on immunology, august 21-26, 2016, Australia; 4th European Immunology events September 6-9, 2015, Austria

Track 11:Immunology and Diabetes

Immunologyis the study of the immune system, which is responsible for protecting the body from foreign cells such as viruses, bacteria and parasites. Immune system cells called T and B lymphocytes identify and destroy these invaders. Thelymphocytesusually recognize and ignore the bodys own tissue (a condition called immunological self-tolerance), but certain autoimmune disorders trigger a malfunction in the immune response causing an attack on the bodys own cells due to a loss ofimmune tolerance.

Type 1 diabetes is anautoimmune diseasethat occurs when the immune system mistakenly attacks insulin-producing islet cells in the pancreas. This attack begins years before type 1 diabetes becomes evident, so by the time someone is diagnosed, extensive damage has already been done and the ability to produceinsulinis lost.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

InternationalConference onMucosalImmunology, July 28-29, 2016, Australia; International Conference onAllergy, March 29-30, 2016, Spain; 2ndInternationalCongress onNeuroimmunology&Therapeutics, Dec 01-03, 2016, USA;7th InternationalConference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands; Asthma EventsSeptember 14-15, 2016 Amsterdam, Netherlands;2nd InternationalConference on Antibodiesand Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; InternationalConference on Tumor Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia; InternationalConference on Cancer Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia; Immunology events InternationalcongressonImmunology, August 21-26, 2016, Australia; British society for Immunology Annual Immunology Congress, 6-9 Dec, 2016, Liverpool, UK

Track 12:Immune Tolerance

Immunological toleranceis the failure to mount animmuneresponse to an antigen. It can be: Natural or "self"tolerance. This is the failure (a good thing) to attack the body's own proteins and other antigens. If the immunesystem should respond to "self",an autoimmune diseasemay result. Natural or "self" tolerance: Induced tolerance: This is tolerance to externalantigens that has been created by deliberately manipulating theimmune system.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

InternationalConference onMucosalImmunology, July 28-29, 2016, Australia; International Conference onAllergy, March 29-30, 2016, Spain; 2ndInternationalCongress onNeuroimmunology&Therapeutics, Dec 01-03, 2016, USA;7th InternationalConference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands; Asthma EventsSeptember 14-15, 2016 Amsterdam, Netherlands;2nd InternationalExhibition on Antibodiesand Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA; InternationalConference on Tumor Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia; InternationalConference on Cancer Immunologyand Immunotherapy, July 28-30, 2016 Melbourne, Australia; Immunology events InternationalcongressonImmunology, August 21-26, 2016, Australia; British society for Immunology Annual Immunology Congress, 6-9 Dec, 2016, Liverpool, UK

Track 13:Vaccines and Immunotherapy

Vaccine is a biological preparation that improves immunity to particular disease. It contains certain agent that not only resembles a disease causing microorganism but it also stimulates bodys immune system to recognise the foreign agents. Vaccines are dead or inactivated organisms or purified products derived from them. whole organism vaccines purified macromolecules as vaccines,recombinant vaccines, DNA vaccines. The immune system recognizes vaccine agents as foreign, destroys them, and "remembers" them. The administration of vaccines is called vaccination. In order to provide best protection, children are recommended to receive vaccinations as soon as their immune systems are sufficiently developed to respond to particular vaccines with additional "booster" shots often required to achieve "full immunity".

Immunotherapy is treatment that uses certain parts of a persons immune system to fight diseases such as cancer. This can be done in a couple of ways:

Stimulating your own immune system to work harder or smarter to attack cancer cells

Giving you immune system components, such as man-made immune system proteins

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

10th Euro Global Summit andExpo on Vaccines & VaccinationJune 16-18, 2016 Rome, Italy; 11th Global Summit andExpo on Vaccines, Vaccination and TherapeuticsSeptember 12-14, 2016 Phoenix, Arizona, USA; 12th Asia Pacific Global Summit andExpo on Vaccines & VaccinationNovember 24-26, 2016 Melbourne, Australia;International Congress of Immunology;7th InternationalConference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands; International Conference on Autoimmunity, October 13-14, 2016 Manchester, UK;World Vaccine CongressApril 10-12, 2017 Washington; 10thVaccine Congress4-7 September 2016, Amsterdam, The Netherlands 10thVaccine Congress, 4-7 September 2016, Amsterdam British society for Immunology Annual Immunology Congress, 6-9 Dec, 2016, Liverpool, UK; 5th European Immunology Conferences, July 21-23, 2016 Berlin, Germany;USA Immunology Conferences

Track 14:Immunologic Techniques, Microbial Control and Therapeutics

Immunological techniques include both experimental methods to study the immune system and methods to generate or use immunological reagents as experimental tools. The most common immunological methods relate to the production and use of antibodies to detect specific proteins in biological samples. Various laboratory techniques exist that rely on the use of antibodies to visualize components of microorganisms or other cell types and to distinguish one cell or organism type from another. Immunologic techniques are used for: Quantitating and detectingantibodiesand/orantigens, Purifying immunoglobulins, lymphokines and other molecules of the immune system, Isolating antigens and other substances important in immunological processes, Labelling antigens and antibodies, Localizing antigens and/or antibodies in tissues and cells, Detecting, and fractionatingimmunocompetent cells, Assaying forcellular immunity, Documenting cell-cell interactions, Initiating immunity and unresponsiveness, Transplantingtissues, Studying items closely related to immunity such as complement,reticuloendothelial systemand others, Molecular techniques for studying immune cells and theirreceptors, Imaging of the immune system, Methods for production or their fragments ineukaryoticandprokaryotic cells.

Microbial control:

Control of microbial growth, as used here, means to inhibit or prevent growth of microorganisms. This control is achieved in two basic ways: (1) by killing microorganisms or (2) by inhibiting the growth of microorganisms. Control of growth usually involves the use of physical or chemical agents which either kill or prevent the growth of microorganisms. Agents which kill cells are called cidal agents; agents which inhibit the growth of cells (without killing them) are referred to as static agents. Thus, the term bactericidal refers to killing bacteria, and bacteriostatic refers to inhibiting the growth of bacterial cells. A bactericide kills bacteria, a fungicide kills fungi, and so on. In microbiology, sterilization refers to the complete destruction or elimination of all viable organisms in or on a substance being sterilized. There are no degrees of sterilization: an object or substance is either sterile or not. Sterilization procedures involve the use of heat, radiation or chemicals, or physical removal of cells.

Related: Immunology Conferences|Immunologists Meetings|Conference Series LLC

2nd international conference on innate immunity, July 21-22, 2016, Germany; 2nd International Conference and Exhibition on Antibodies and Therapeutics, July 11-12, 2016 Philadelphia, Pennsylvania, USA;7th InternationalConference on Allergy, Asthma and Clinical Immunology, September 14-15, 2016 Amsterdam, Netherlands, September 14-15, 2016 Amsterdam, Netherlands;International Conference on Autoimmunity, October 13-14, 2016 Manchester, UK; Immunology 2016, American Association of Immunologists, Annual MeetingMay 13-17, Los Angeles, USA;9th EuropeanMucosal Immunology meetings, October 9 - 12 October, Scotland;

Track 15:Immunodeficiency

Immunodeficiency is a state in which theimmune system's ability to fightinfectious diseaseis compromised or entirely absent. Immunodeficiency disorders prevent your body from adequately fighting infections and diseases. An immunodeficiency disorder also makes it easier for you to catch viruses and bacterial infections in the first place. Immunodeficiency disorders are often categorized as either congenital or acquired. A congenital, or primary, disorder is one you were born with. Acquired, or secondary, disorders are disorders you get later in life. Acquired disorders are more common thancongenital disorders. Immune system includes the following organs: spleen, tonsils, bone marrow, lymph nodes. These organs make and release lymphocytes. Lymphocytes are white blood cells classified as B cells and T cells. B and T cells fight invaders called antigens. B cells release antibodies specific to the disease your body detects. T cells kill off cells that are under attack by disease. An immunodeficiency disorder disrupts your bodys ability to defend itself against these antigens. Types of immunodeficiency disorder are Primary immunodeficiency disorders & Secondary immunodeficiency disorders.

Primary immunodeficiency disorders are immune disorders you are born with. Primary disorders include:

X-linked agammaglobulinemia (XLA)

Common variable immunodeficiency (CVID)

Severe combined immunodeficiency(SCID)

Secondary disorders happen when an outside source, such as a toxic chemical or infection, attacks your body. Severe burns and radiation also can cause secondary disorders.

Link:
Worlds Leading Immunology Congress | Conferenceseries

AJRCCM – Home (ATS Journals)

By adminOctober 16, 2016Uncategorized

This site uses cookies to improve performance. If your browser does not accept cookies, you cannot view this site.

There are many reasons why a cookie could not be set correctly. Below are the most common reasons:

This site uses cookies to improve performance by remembering that you are logged in when you go from page to page. To provide access without cookies would require the site to create a new session for every page you visit, which slows the system down to an unacceptable level.

This site stores nothing other than an automatically generated session ID in the cookie; no other information is captured.

In general, only the information that you provide, or the choices you make while visiting a web site, can be stored in a cookie. For example, the site cannot determine your email name unless you choose to type it. Allowing a website to create a cookie does not give that or any other site access to the rest of your computer, and only the site that created the cookie can read it.

Read more here:
AJRCCM - Home (ATS Journals)

Stem Cell Basics VI. | stemcells.nih.gov

By adminOctober 12, 2016Induced Pluripotent Stem Cells

Induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to an embryonic stem celllike state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. Although these cells meet the defining criteria for pluripotent stem cells, it is not known if iPSCs and embryonic stem cells differ in clinically significant ways. Mouse iPSCs were first reported in 2006, and human iPSCs were first reported in late 2007. Mouse iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cells from all three germ layers, and being able to contribute to many different tissues when injected into mouse embryos at a very early stage in development. Human iPSCs also express stem cell markers and are capable of generating cells characteristic of all three germ layers.

Although additional research is needed, iPSCs are already useful tools for drug development and modeling of diseases, and scientists hope to use them in transplantation medicine. Viruses are currently used to introduce the reprogramming factors into adult cells, and this process must be carefully controlled and tested before the technique can lead to useful treatment for humans. In animal studies, the virus used to introduce the stem cell factors sometimes causes cancers. Researchers are currently investigating non-viral delivery strategies. In any case, this breakthrough discovery has created a powerful new way to "de-differentiate" cells whose developmental fates had been previously assumed to be determined. In addition, tissues derived from iPSCs will be a nearly identical match to the cell donor and thus probably avoid rejection by the immune system. The iPSC strategy creates pluripotent stem cells that, together with studies of other types of pluripotent stem cells, will help researchers learn how to reprogram cells to repair damaged tissues in the human body.

Previous|VI. What are induced pluripotent stem cells?|Next

Originally posted here:
Stem Cell Basics VI. | stemcells.nih.gov