Stem Cell Clinic

Somatic stem cells in the human endometrium.

By adminOctober 7, 2016Somatic Stem Cells

The existence of human endometrial somatic stem cells was proposed in the mid-20th century for the first time. This hypothesis became stronger and was revised by two authors between 1978 and 1989. Nevertheless, it was not until 2004 that scientific evidence was first published. As we describe here, the great regenerative capability of the human endometrium has been finally questioned in the last 8 years, and this period can be considered the most productive in endometrial stem cell biology given the new scientific information recapitulated to date. We provide a detailed summary based on the actual scientific knowledge obtained about (1) the existence of somatic stem cells in murine (detected with label-retaining cell methods) and human (cells isolated by different methods) endometria, (2) the involvement of bone marrow as a putative extrauterine source of endometrial somatic stem cells, (3) the implication and biological pathways of these cells in several pathologies like endometriosis and endometrial cancer, and (4) the future of endometrial somatic stem cells in regenerative medicine to provide new strategies in autologous transplant and bioengineering.

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Miller School of Medicine | University of Miami

By adminOctober 7, 2016Stem Cell Medical Center

Researchers Innovative Study Links Sustained Poverty to Worse Cognitive Function in Midlife

From left, Adina Zeki Al Hazzouri, Ph.D., with Tali Elfassy, M.S.P.H.

Sustained exposure to economic hardship over two decades was strongly associated with worse cognitive function in relatively young individuals, according to a recent study led by Adina Zeki Al Hazzouri, Ph.D., assistant professor of Epidemiology in the Department of Public Health Sciences at the University of Miami Miller School of Medicine.

Zeki Al Hazzouri, Ph.D., was lead author of the article, Sustained Economic Hardship and Cognitive Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study, published recently in the American Journal of Preventive Medicine. Her Miller School co-author was Tali Elfassy, M.S.P.H., a Ph.D. candidate in Epidemiology. The studys co-authors are Stephen Sidney, M.D., M.P.H., of Kaiser Permanente in Oakland, Calif.; David Jacobs, Ph.D., of the University of Minnesota in Minneapolis; Eliseo J. Perez Stable, M.D., of the National Institute of Minority Health and Health Disparities in Bethesda, and Kristine Yaffe, M.D., from the University of California San Francisco.

Stem Cell | Makise Medical Center Japan

By adminOctober 5, 2016Stem Cell Medical Center

Cells develop from only one fertilized egg --- zygote. A "Totipotent Cell" with the ability to differentiate into more than 220 cell types. except placenta. But its Totipotency, (which represents the cell with the greatest differentiation potential) is not retained during all the various stages of cell sub-division.

The first sub-division provides 2 Totipotent cells. The second 4 cells, retain Totipotency But the following 8 cells no longer retain the ability to differentiate into all types of cells. Further sub-divisions differentiate into specialized cells such as fibroblasts, erythrocytes, nerve cells, intestinal mucosal epithelial cells and pancreatic islet cells, etc. but following 6 to 7 full further cell sub-divisions (about 5 days after fertilization), the embryo becomes a "Blastocyst" and possesses "Inner Cell Mass (ICM) "

ICM cells can differentiate into any cell type, except placenta --- pluripotency. 3 weeks after fertilization, the cells of the inner cell mass differentiate into ectoderm, mesoderm and endoderm. In the 1950s, this differentiation was thought to be irreversible, being described as a ball rolling down a hill and technically known as " Epigenetic Landscape".

This was until 1962 when John Gurdon created clone frogs and then in 1996 Ian Wilmut created "Dolly " the cloned sheep. Scientists had previously thought stem cells could not have pluripotency once dispersed into a specialized cell. however, in nature, even once differentiated, some cells can again differentiate and this phenomenon is known to science.

The stem cells of humans have limited ability to differentiate. But for example, Planaria that is a small flatworm living in rivers has amazing ability to differentiate into any organs, even into itself. When it is chopped into 3 fragments like picture, each fragment regenerates to a perfect Planaria. There is a record that 1/279 fragment of one Planaria regenerated to perfect Planarias. When Planaria grows to a certain size, it divides itself to two fragments. And each fragment grows to a perfect Planaria. For Planaria, division and regeneration are mechanism for reproduction. But under some circumstances Planaria chooses sexual reproduction.

A Plant can regenerate itself from one already differentiated cell. An Enzyme mixture of Cellulase Onozuka R-10 and Macerozyme R-10 dissolves tobacco plant (Nicotiana tabacum) leaf cell walls, and cells become leaf protoplasts (= cell without cell walls). When protoplasts are cultivated under appropriate condition, the protoplasts grow to a seedling plant through plant callus (= mass of unorganized parenchyma cells). When the seedling plant is planted in soil, it grows to a perfect tobacco plant.

Two British scientists proved biological technique could change Epigenetic Landscape.

Gurdon created cloned frogs.

Wilmut used a cell nucleus which had been differentiated in the mammary gland.

Human embryos reach "Blastocyst" about 5 days' post fertilization. The Blastocyst possesses an "Inner Cell Mass (ICM) " In 1981 Martin Evans succeeded in culturing mouse ICM cells. These cells are capable of propagating themselves indefinitely in an undifferentiated state, and they can differentiate into any type of cell except placenta. These cells are pluripotent, and known as Embryonic Stem Cell (ES Cells). James Thomson created ES Cells from Monkey embryo in 1995 and later in 1998 created ES Cells from human embryo. However, research into ES Cell needs further study due to an ethical dilemma, that in order to isolate inner cells from the blastocyst, the blastocyst is destroyed, so is the embryo at pre-implantation stage to be considered human? and even if not, do we have the right to destroy human potential growth.

The ethical issue of ES Cells can be by-passed by using Induced pluripotent stem cells. The iPS cell is a pluripotent stem cell which can be generated directly from adult cells, not from human embryos, and in 2006, Shinya Yamanaka and his team in Kyoto University created iPS cells from mouse fibroblasts.

He hypothesized that the genes playing a pivotal role in the function of ES Cells could induce an embryonic state in adult cells. But how many are the genes? The human has 20 - 25 thousand genes. Yamanaka researched and found 24 genes which were important for the characteristic protein of human ES Cells, and then used retroviruses to deliver all 24 genes into mouse fibroblasts, and the fibroblasts were able to propagate indefinitely. These iPS Cells were pluripotent like ES Cells.

Yamanaka removed one factor at a time from the 24 factors to identify the necessary genes for reprogramming and by this process he identified 4 factors -- Oct3/4, Sox2m Klf4 and c-Myc - named the "Yamanaka Factors", and Later he found c-Myc was not needed for reprogramming, but without c-Myc the process took longer and was inefficient.

A strong concern of the iPS researchers was if iPS Cell differentiation caused cancerous cells. But this issue has almost been resolved completely through rigorous study. And many clinical human applications are now carried out in Japan. For example, in 2014 retina transplantation by iPS Cells was successfully carried out for age-related macular degeneration. And cells did not differentiate into cancer cells. In my next page, I write more about these applications.

iPS Cells are useful not just for regenerative medicine but for drug discoveries or development. Because it is very easy for researchers to recreate special cells which cause special diseases, in a petri dish --- Alzheimer's disease, Parkinsons disease, ALS (Amyotrophic Lateral Sclerosis), Schizophrenia.

For example, "Achondroplasia" which is caused by mutation in fibroblast growth factor receptor 3. This is a common cause of dwarfism. Researchers made iPS Cells from skin fibroblasts of 3 patients with achondroplasia then allowed the iPS Cells to differentiate into chondrocytes over 2 to 3 weeks. Chondrocytes in the petri dish secreted about themselves an extracellular matrix which is characteristic of chondrocytes and made a mass. Compared to the chondrocytes of healthy people, these patients chondrocytes grew slowly, and the researchers tried thousands of drugs one by one to cure the abnormal chondrocytes from the petri dish specimens. Then finally, and with much surprise, they found the "Statin drug" was effective and able to cure the abnormal chondrocytes of achondroplasia patients. Why surprise? Because Statin drugs are for lowering cholesterol, and nobody expected cholesterol lowering drugs to be effective against achondroplasia.

In the next pages I explain in more detail about practical and clinical uses of iPS Cells.

The researchers of iPS Cells were most afraid of differentiation of iPS Cells into cancer cells. But now this problem has been almost solved by rigorous studies. And many clinical applications for humans are being done in Japan. For example, in 2014 transplantation of iPS Cells of retina was successfully done for age-related macular degeneration in Japan. The cells have not differentiated into cancer cells. In the next page, I write more about the applications.

iPS Cell is very useful not only for regeneration medicine but also for drug discovery or drug development. Because it is very easy for researchers to make the special cells that cause the special diseases --- Alzheimer's disease, Parkinson's disease, ALS (Amyotrophic Lateral Sclerosis), Schizophrenia -- in petri dish.

For example, Achondroplasia that is caused by a mutation in fibroblast growth factor receptor 3. This is a common cause of dwarfism. The researchers made iPS Cells from the skin fibroblasts of the 3 patients of achondroplasia and let the iPS Cells differentiate into chondrocytes in 2 to 3 weeks. The chondrocytes in petri dish secreted around themselves an extracellular matrix that is characteristic of chondrocytes and made a mass. The chondrocytes from the patients grow very slow compared with the chondrocytes from those of healthy people. The researchers tried thousands of drugs one by one to cure abnormal chondrocytes from the patients in petri dish. Then finally, and with much surprise, they found "Statin drug" was effective to cure the abnormal chondrocytes of achondroplasia patients. Why surprise? Because Statin drugs are drugs for cholesterol lowering. Nobody expected cholesterol lowering drugs are effective for achondroplasia.

In the next pages, I explain in more detail about practical and clinical use of iPS Cells.

Adult Stem Cells are undifferentiated cells found throughout the body such as in bone marrow, and umbilical cord blood, and the mammary gland, and the surface of the small and large intestines, the adipose tissue, the lining of the nose, the testicles, and the hair follicle, between the basement membrane and the sarcolemma of muscle fibers (Satellite Cells), etc.

These cells are multipotent cells that have less ability to differentiate into specialized cells than pluripotent cells. The adult stem cell from the bone marrow, called Hematopoietic Stem Cell (HSC), was discovered in the 1960s by two Canadian biologists, James Till and Ernest McCulloch, and has been used clinically to cure various blood diseases, such as leukemia, malignant lymphoma, multiple myeloma, etc. Clinically a very important cell. But for regenerative medicine, it needs much practical work to obtain stem cells from bone marrow, and requires general anesthesia, however scientists recently have found it easier to obtain these cells.

This is by ASC (adipose-derived stem cell) from our fat. The first scientific reports on ASC were made by an American scientist, Patricia Zuk (UCLA), in 2001. She reported the presence of mesenchymal stem cells in the fat tissues, and as they have a faster growth rate, these cells are expected to be advantageous for regenerative medicine.

ASC can differentiate into muscle, bone, cartilage, liver, adipose cell (lipid cell). And besides the advantages as stem cell, ASC secrets exsosome (nano size particles) that contain enzymes which dissolve beta-amyloid of Alzheimer's disease. The efficacy is 8 times more potent than the enzymes secreted by the exssome of the bone marrow.

ASC is now aggressively researched in Japan for practical uses. It will be used to treat many diseases such as Alzheimer's, Parkinson's, and diseases of the liver and kidneys, and periodontal disease, and more. For example, please see the video:

In Japan Tottori University Medical School researchers have established the technique of breast reconstruction by ASC after mastectomy due to cancer. They operate and inject ASC into the patients depressed breast. The breast recovers to the original shape within three months. This is not silicon, but the patients own cells. Quite natural. No rejection. The cost of this treatment will be covered by health insurance within three years in Japan. And Doctors at the Nagoya University Medical School use ASC against urinary incontinence stress. The sphincter function of the urethra often weakens due to aging,delivery, and some bladder diseases. ASC is injected around the patients urethra to strengthen the smooth muscle.

However, some side effects may occur by use of ASC. For example, male prostate hyperplasia and female endometriosis. Issues not studied in depth. So for now until the side effects have been dealt with, we should wait for general anti-aging treatments.

Recently it was found possible to induce, directly from somatic cells, not only iPS but nerve cells, hepatocyte cells, myocardium cells, cartilage cells, and many varied cells by introducing the specific key transcription factors in cell differentiation, which means that through by-passing of pluripotent stem cells it is possible to induce differentiated specific cells from somatic cells. This is called "Direct Reprogramming", and the most exciting research for example is: myocardial reprogramming in vivo, where Doctors inject patient's fibroblasts with transcription factors to the infarcted lesion of the heart. There the fibroblasts differentiate into myocardium (heart muscle). So, simple and quick. And this regenerative medical technique is under development mainly in Japan and the United States and as this technique is established, lots of heart surgeries will become obsolete and this is also true of brain surgery. The numbers of hospitals will eventually reduce and cost of time consuming surgeries will lower and this will lead on to a "De-Hospitalized Society".

For a basic understanding of stem cell mechanisms: ES Cell is studied along with iPS Cell and ASC. But ES Cell has an ethical dilemma and this issue shall not be overcome by science. So, it cannot be used for the treatment of human diseases. Direct Reprogramming: Wonderful technology. But it may take 10 or 20 years more to accomplish it. Therefore, at this moment, iPS Cell and ASC are most realistic medical tools for those who are suffering from degenerative diseases and wish rejuvenation.

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Stem Cell | Makise Medical Center Japan

Embryonic Stem Cells | Stem Cells Freak

By adminOctober 4, 2016Embryonic Stem Cells

As their name suggests, embryonic stem cells (ESCs) are stem cells that are derived from embryos. If we wanted to be more scientific, we would say that ESCs are pluripotent stem cells derived from a blastocyst, an embryo in a very early stage (4-5 days of age).A blastocyst is consisted of 50-150 cells. ESCs measure approximately 14m in diameter.

The use of human embryonic stem cells is highly controversial, as their extraction requires the destruction of a human embryo, raising a great number of ethical issues. The main one is whether a blastocyst can be considered a living person or not. Check our article, Stem Cell Controversy for more info on this topic

Embryonic Stem cell properties There are two important attributes that distinguish stem cells from any other typical cell:

Embryonic stem cells are pluripotent, having the capacity to differentiate and develop into almost all kinds of cells belonging to thethree primary germ layers:

As for self-renewal, ES cells have the capacity to replicate indefinitely. In other words they have the ability, under the proper conditions, to produce infinite numbers of daughter cells just from one or a few father cells.

Human Embryonic Stem Cell Extraction And Culture First the inner cell mass (ICM) of the blastocyst is separated from the trophectoderm. Then the cells of the ICM are placed on aplastic laboratory culture dish that contains a nutrient broth called the "culture medium". Typically the inner surface of the dish is coated with what is called a "feeder layer", consisting of reprogrammed embryonic mouse skin cells that don't divide. These mouse cells lay in the bottom of the dish and act as a support for the hESCs. The feeder layer not only provides support, but it also releases all the needed nutrients for thehESCs to grow and replicate. Recently, scientists have devised new ways for culturing hESCs without the need of a mouse feeder cell, a really important advance as there is always the danger of viruses being transmitted from the mouse cells to the human embryonic stem cells.

It should be noted that the process described above isn't always successful, and many times the cells fail to replicate and/or survive. If on the other hand, the hESCs do manage to survive and multiply enough so that the dish is "full", they have to be removed and plated into several dishes. This replating and subculturing process can be done again and again for many months. This way we can get millions and millions of hESCs from the handful ones we had at the beginning.

At any stage of the process, a batch of hESCs can be frozen for future use or to be sent somewhere else for further culturing and experimentation.

How are human embryonic stem cells induced to differentiate ? There are various options for researchers to choose from, if they decide to differentiate the cultured cells.

The easiest one, is to simply allow the cells to replicate until the disc is "full". Once the disc is full, they start to clump together forming embryoid bodies(rounded collections of cells ). These embryoid bodies contain all kinds of cells including muscle, nerve, blood and heart cells. As said before, although this is easiest method to induce differentiation, it is the most inefficient and unpredictable as well.

In order to induce differentiation to a specific type of cell, researchers have to change the environment of the dish by employingone of the ways below:

Human Embryonic Stem Cells, potential uses Many researchers believe that studying hESCs is crucial for fully understanding the complex events happening during the fetal development. This knowledge would also include all the complex mechanisms that trigger undifferentiated stem cells to develop into tissues and organs. A deeper understanding of all these mechanisms would in return give scientists a deeper understanding of what sometimes goes wrong and as a result tumours,birth defects and other genetic conditions occur, thus helping them to come up with effective treatments.

Several new studies also address the fact that human embryonicstem cells can be used as models for human genetic disorders that currently have no reliable model system. Two examples are the Fragile-X syndromeandCystic fibrosis.

As of now, there has been only one human clinical trial ,involving embryonic stem cells, with the officialapproval of the U.S. Food and Drug Administration (FDA).The trial started on January 23, 2009, and involved the transplantation ofoligodendrocytes (a cell type of the brain and spinal cord) derived from human embryonic stem cells. During phase I of the trial, 8 to 10paraplegics with fresh spinal cord injuries (two weeks or less) were supposed to participate.

In August 2009,the trial wasput on hold, due to concerns made by the FDA, regarding a small number of microscopic cysts found in several treated rat models. InJuly 30, 2010 the hold was lifted and researchers enrolled the first patient and administered him with the stem cell therapy.

See the article here:
Embryonic Stem Cells | Stem Cells Freak

Japanese scientist wins 2016 Nobel medicine prize | Reuters

By adminOctober 3, 2016Uncategorized

By Niklas Pollard and Kate Kelland | STOCKHOLM/LONDON

STOCKHOLM/LONDON Japan's Yoshinori Ohsumi won the 2016 Nobel prize for medicine for ground-breaking experiments with yeast which exposed a key mechanism in the body's defenses where cells degrade and recycle their components.

Understanding the science behind the process, called "autophagy" or "self-eating", has led to a better understanding of diseases such as cancer, Parkinson's and type 2 diabetes, the prize committee said in its statement on Monday.

"Ohsumi's discoveries led to a new paradigm in our understanding of how the cell recycles its content," it said.

The Physiology or Medicine prize, the first of the Nobel prizes awarded each year, is worth 8 million Swedish crowns ($933,000).

Ohsumi, born in 1945 in Fukuoka, Japan, has been a professor at the Tokyo Institute of Technology since 2009. He told Kyodo News agency he was "extremely honored" to get the prize.

In a separate interview with broadcaster NHK, he said he had "always wanted to do something that other people wouldnt do".

"I thought the breakdown (of cells) would be interesting, and that was my start," he said.

Ohsumi's work - carried out in the 1990s and described by commentators as "paradigm-shifting" and "pioneering" - included locating the genes that regulate autophagy. This is important for medicine because it helps show why errors in these genes can contribute to a range of diseases.

David Rubinsztein, deputy director of Cambridge University's Institute for Medical Research, said Ohsumi had provided scientists around the world with "critical tools" to help them understand how disrupted autophagy can contribute to illnesses including infectious diseases, cancers and neurodegenerative diseases such as Huntingtons and Parkinsons.

Chister Hoog, a professor at Sweden's Karolinska Institute, told Reuters the work helped explain crucial processes in human development, from growing up, to aging to succumbing to disease.

"In the very early stages (of a humans development) your organs and your whole body is constantly being made over again you are growing. So you need to get rid of the old stuff and generate new structures," he said.

"When you undergo aging, you have structures that have to be taken away and this autophagy is the principle that gets rid of them.

"If you affect this system the genes and proteins involved in autophagy you no longer can take care of the waste, and once it accumulates you will get some type of disease."

This year, the Karolinska Institute, which awards the Nobel medicine prize, has been immersed in a scandal over the hiring of a controversial surgeon. The Swedish government dismissed several members of the board in September.

Prizes for achievements in science, literature and peace were first awarded in 1901 in accordance with the will of dynamite inventor and businessman Alfred Nobel. ($1 = 8.5776 Swedish crowns)

(This version of the story fixes the typo in the name of the Karolinska professor)

(Additional reporting by Stockholm Newsroom and by Minami Funakoshi in Tokyo; Editing by Alistair Scrutton and Robin Pomeroy)

SAN FRANCISCO California will allow companies more leeway in testing self-driving cars on public roads while restricting how the nascent technology is advertised under revised draft regulations released on Friday.

German luxury auto maker BMW AG said on Friday it will offer all electric versions of its next generation BMW X3 compact sport utility vehicle and electric Mini models, expanding its entries in the emerging electric luxury vehicle market.

BRUSSELS U.S. software company Salesforce called on EU regulators on Thursday to investigate antitrust issues related to Microsoft's $26 billion bid for social network LinkedIn.

Continued here:
Japanese scientist wins 2016 Nobel medicine prize | Reuters

Hematology Conferences | Blood Disorder Conferences | USA …

By adminOctober 3, 2016Uncategorized

6thInternational Conference on Hematology

Date:October 03-05, 2016

Venue:Orlando, Florida, USA

Hematology 2016 has been designed with many interesting and informative scientific sessions; it includes all possible aspects of Hematology research.

Hematology

Erythrocytesare also known as red blood cells which carry oxygen to the body and collect carbon dioxide from the body by the use of hemoglobin and its life span of 120 days. along the side the leucocytes helps in protecting the healthy cells because the W.B.C (leucocytes) act as the defending cells in protecting the immune system from the foreign cells. Theseleucocytesare multipotent cells in bone marrow and there life span is of 3-4 days where the yellow blood cells are called as thrombocytes they are where small and irregular in shape they have life span of 5-9 days they are mostly seen in mammals they help in clotting of blood which are in fibrin form called as thrombosis these lead to heart stroke, blockage of blood in blood mostly in arms and legs. where C.B.C is known ascomplete blood countis done to know the number of cells in a body these are mainly done by lab technician presently they are been tested by automatic analyzer the high and low amount of cells will lead to many diseases. Decrease of R.B.C in the body these causes of anemia which leads to weakness, feeling of tired, shortness of breath and person will be noticeably pale. Formation of blood cellular components are called as Hematopoiesis and all the cellular blood components are derived from hematopoiesis stem cells in a healthy individual nearly 10111012new blood cells are produced these help in steady peripheral circulation. If there is a increases of R.B.C in the body these causes polycythemia these can be measured through hematocrit level.

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International Conference onGenetic CounselingandGenomic MedicineAugust 11-12, 2016, UK; International Conference onClinicalandMolecular GeneticsNovember 28-30, 2016, USA; 5thInternational Conference and Exhibition onCellandGene TherapyMay 19-21, 2016, USA; World Congress onHuman GeneticsOctober 31- November 02, 2016, Spain; International Conference onNext Generation SequencingJuly 21-22, 2016, Germany; 58th ASH Annual Meeting & Exposition December 3-6, 2016 San Diego, CA; ESH 2016 Annual Meeting June 10 13, 2016 Paris, France; ASH Conferences on Lymphoma Biology June 18 - 21, 2016 ESH 5th International Conference on Myelodysplastic Syndromes April 14 April 16, 2016 Estoril, Portugal; European Society ofHuman Genetics: ESHG Conferences May 21-24, 2016, Spain; American Society ofHuman Genetics;ASHG Annual Meeting October 6-10, 2015, Maryland.

Blood Disorders

Hemophilia Ais a genetic deficiency in clottingfactor VIII,which causes increased bleeding and usually affects males. About 70% of the time it is inherited as an X-linked recessive trait, but around 30% of cases arise from spontaneous mutations. Hemophilia B is ablood clottingdisorder caused by amutationof thefactor IXgene, leading to a deficiency of factor IX. It is the second-most common form ofhaemophilia, rarer thanhaemophilia A. It is sometimes calledChristmas disease, named afterStephen Christmas, the first patient described with this disease.In addition, the first report of its identification was published in the Christmas edition of theBritish Medical Journal.Hemophilia C is a mild form of haemophiliaaffecting both sexes. However, it predominantly occurs in Jews ofAshkenazidescent. It is the fourth most common coagulationdisorder aftervon Willebrand's diseaseandhaemophiliaAandB.In theUSAit is thought to affect 1 in 100,000 of the adult population, making it 10% as common as haemophilia A. Idiopathic thrombocytopenic purpura(ITP), also known asimmune thrombocytopenia,primary immune thrombocytopenia,primary immune thrombocytopenic purpuraorautoimmune thrombocytopenic purpura, is defined as isolated low platelet count (thrombocytopenia) with normalbone marrowand the absence of other causes of thrombocytopeniaVon Willebrand diseasesis the most common hereditarycoagulationabnormality described in humans. Platelets also called "thrombocytes" areblood cellswhose function (along with thecoagulation factors) is to stop bleeding by clumping and clogging blood vessel injuries.Platelets have nocell nucleus: Coagulation is highlyconservedthroughout biology; in allmammals, coagulation involves both a cellular (platelet) and aprotein(coagulation factor) component and these are occoured due togenetic blood disorders

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6thInternational Conference onHematologyOctober 03-05, 2016 Orlando, Florida, USA;4thInternational Conference onBlood Malignanciesand TreatmentApril 18-19, 2016, UAE;International Conference onLeukemiaandBone marrow TransplantationNovember 10-12, 2016 Turkey; 7thHealth Careand Fitness SummitSeptember 26-28, 2016, UK; NHF 67th Annual Meeting, Dallas, August 13-15, 2015 USA; European HemophiliaConsortium: EHC Conference, 02-04 October 2015, Serbia;ASH Meeting on Lymphoma Biology June 18 - 21, 2016 Colorado Springs, CO; Hemophilia& Thrombosis Research Society : HTRS Scientific Symposium, 25-26 November 2015, USA ; Society ofThrombosis and Haemostasis Research: GTH Annual Meeting 1 7- 20 Feb 2016, Germany ; American Society ofHematology: ASH Annual Meeting & Exposition December 5-8, 2015 USA ESH 7th International Conference on Myeloproliferative Neoplasms October 27 - October 29, 2016 Estoril, Portugal

Hematologic Malignancies

Lymphatic leukemiawhich effect the white blood cells(w.b.c) they are closely related to the lymphomas and some of them are unitary diseases which related to the adult T cells leukemia these come under the lymphoproliferative disorders. Mostly they involve in the B-cell sub type lymphocytes. The myeloid leukemia is preferred to the granulocyte precursor in the bone marrow and spinal cord and these arises the abnormal growth in the blood from tissues in the bone marrow. They are mainly related to the hematopoietic cells and these sub title into acute and chronic lymphoblastic leukemia. The acute leukemia is that rapidly producing immature blood cells as they are bulk number of cells healthy cells are not produced in bone marrow due this spill over the blood stream which spread to other body parts. Where as in chronic leukemia highly bulid of matured cells are formed but still abnormal white cells are formed these can not be treated immediately mostly seen in older people. The cancer which originate from white blood cells are called as lymphoma and this disorder is mainly seen inHodgkin lymphomathese diseases is treated by radiation and chemotherapy, orhematopoietic stem cell transplantation. The cancer which starts with in the cell are called as Non Hodgkin lymphocytes and these lymphocytes are of lymph nodes. The bone marrow which develops too many white blood cells leads tomultiple myleoma. The further details on malignance are been discussed inHematology oncology conference-2015.

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4thInternational Conference onBlood Malignancies& Treatment April 18-20 2016,UAE ; 5thworld Hematologists Congress June 06-08 2016,UK ; International Conference onLeukemiaandBone marrow TransplantationNov 10-12 2016, Turkey ; 8thEuro Global Summit onCancer TherapyNovember 03-05 2015,Spain; 10thGlobal AnnualOncologists MeetingJuly 11-13 2016, Germany;6thInternational Conference onHematology October 03-05, Orlando, Florida USA; Global Summit & Expo onHealth careNovember 9-11 2015,UAE ; International Conference onInternal MedicineNovember 03-05, 2016 ,USA ; ASH Meeting on Hematologic Malignancies September 15 - 17, 2016 Chicago, IL; ESH Conferences: 18th Annual John Goldman Conference onChronic Myeloid Leukemia: Biology and Therapy, Sep 15 - 18, 2016, US; The 26thRegional congress of the ISBT November 14-16 2015, Indonesia ; Texas Bleeding Disorders Conference November 8 2015 ,Texas ; ASH 3rd International Conference on Multiple Myeloma October 07 - October 09, 2016 Milan, Italy; 7th International Hematologic Malignancies Conference: Bridging the Gap February 27-28, 2016, China; 14th International Conference onMalignant Lymphoma, Jun 14-17,2016; 6th ESMOSarcoma& GIST Conference, 16-17 February 2016, Italy; International Conference onAgingand Hematological Malignancies: Biology and Therapy ,March 11 - March 13, 2016, Greece; ESH 2nd International Conference on New Concepts in B-Cell Malignancies, September 09 - 11, 2016, Portugal.

Hematology and immunology

Blood groupsare of ABO type and but at present the Rh blood grouping of 50 well defined antigens in which 5 are more important they are D,C,c,E and e and Rh factors are of Rh positive and Rh negative which refers to the D-antigen. These D-antigen helps in prevention of erythroblast fetalis lacking of Rh antigen it defined as negative and presences of Rh antigen in blood leads to positive these leads to rh incompatibility. The prevention treatment of diseases related to the blood is called as the Hematology. The hematologists conduct works on cancer to. The disorder of immune system leading to hypersensitivity is called asClinical Immunologyand the abnormal growth of an infection are known as Inflammation and the arise of an abnormal immune response to the body or an immune suppression are known as Auto immune disorder. The stem cell therapy is used to treat or prevent a disease or a condition mostly Bone marrow stem cell therapy is seen and recently umbilical cord therapy Stem cell transplantation strategies remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases.

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International Conference onMucosalImmunology, July 28-29, 2016, Australia; International Conference onAllergy, March 29-30, 2016, Spain; 2nd International Congress onNeuroimmunology&Therapeutics, March 31-Apr 2, 2016, USA; 2nd International Conference onInnate Immunity, July 21-22, 2016, Germany; EuropeanImmunologyConference, July 21-23, 2016, Germany; 9th EuropeanMucosal ImmunologyGroup Meeting, October 9 - 12 October, Scotland; International congress onImmunology, August 21-26, 2016, Australia; International Symposium On B Cells:ImmunityAndAutoimmunity, 1-3 October, 2015, Erlangen, German; 4th European Congress ofImmunologySeptember 6-9, 2015, Austria.

Blood Transplantation

Theumbilical cordis a conduit between the developingembryoorfetusand theplacenta. The umbilical vein supplies the fetus with nutrient-richbloodfrom theplacenta The hematopoitic bone marrow transplant, the HSC are removed from a large bone of the donor, typically thepelvis, through a largeneedlethat reaches the center of the bone. Acute myeloid leukemia is a cancerof themyeloidline of blood cells, characterized by the rapid growth of abnormalwhite blood cellsthat accumulate in thebone marrowand interfere withthe production of normal blood cells and the Thrombosis is the formation of ablood clot inside ablood vessel, obstructing the flow ofbloodthrough thecirculatory system. TheHemostaticis a process which causes bleeding to stop, meaning to keep blood within a damaged blood vessel this is the first stage of wound healing. Metabolic syndromeis a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions, obesity,elevated blood pressure,elevated fasting plasma glucose,high serum triglycerides, and lowhigh-density lipoprotein(HDL) levels. Metabolic syndrome increases the risk developingcardiovascular diseaseanddiabetes.

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6thInternational Conference on Hematology at Florida, USA October 03-05, 2016. 4thInternational conference onBlood malignanceand TreatmentatUAE from April 18-19, 2016. Global Summit onMelanomaand Carcinoma at Australia from July 14-15, 2016.Cancer DiagnosticsConference & Expoat Rome, Italy from June 13-15, 2016. 2nd International Conference and Exhibition onMolecular Medicineand Diagnostics, at USA from September 26-28, 2016. Society forHaematologyandstem cells44th annual scientific meeting 2015, atJapan from September 17-19, 2015. Hellenic Society ofHaematology 26thNational Congress 2015 at Athens from November 12th14th, 2015. British Society forHaemostasisand Thrombosis Annual Meeting 2015 at UK from November 12th-14th, 2015. Society for Immunotherapy of Cancer's Advances inCancer Immunotherapy2015 at USA on December 4th2015. American Society ofHaematology57th Annual Meeting 2015 at USA from December 5th 8th, 2015. Scripps 36th Annual ConferenceClinical Haematology& Oncology 2016 at USA from February 13th 16th, 2016.

Diagnosis and Treatment

Palliative careis amultidisciplinary approachto specialisedmedical carefor people with seriousillnesses The spleen, similar in structure to a largelymph node, acts as a blood filter. Anticoagulants(antithrombics) are a class of drugs that work to prevent thecoagulation(clotting) of blood. Some anticoagulants are used in medical equipment, such astest tubes ,blood transfusionbags, andrenal dialysisequipment. Anvena cava filteris a type of vascular filter, amedicaldevice that is implanted byinterventional radiologistsor vascular surgeons into theinferior vena cavato presumably prevent life-threateningpulmonary emboliistherapyusingionizing radiation, generally as part of cancer treatmentto control or killmalignantcells. Radiation therapy may be curative in a number of types of cancer if they are localized to one area of the body. The subspecialty ofoncologythat focuses on radiotherapy is calledradiation oncology. Translational research is another term fortranslated researchandtranslational science, Applying knowledge from basic science is a major stumbling block in science, partially due to the compartmentalization within science. Targeted drug delivery is a method of deliveringmedicationto a patient in a manner that increases theconcentrationof the medication in some parts of the body relative to others.

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5thInternational Conference and Exhibition onCellandGene TherapyMay 19-21, 2016, USA; International Conference onLeukemiaandBone marrow TransplantationNovember 10-12, 2016 Turkey; World Congress onHuman GeneticsOctober 31- November 02, 2016, Spain; International Conference onNext Generation SequencingJuly 21-22, 2016, Germany; International Conference onClinicalandMolecular GeneticsNovember 28-30, 2016, USA; 11th Annual Cell &Gene TherapyForum 26 -28 February 2016 UK; 17th International Conference on Cell andGene TherapyParis, France; July 20 - 21, 2015; 9th AustralasianGene TherapySociety Meeting (AGTS) 13 - 16 May 2015 Australia; European Society ofHuman Genetics: ESHG Conferences May 21-24, 2016, Spain; 19th Training Course on HaemopoieticStem Cell TransplantationMay 21-23, 2015, Spain

New Drug Development in Haematology

The development of antibiotic resistance in particular stems from the drugs targeting only specific bacterial molecules. Because the drugisso specific, any mutation in these molecules will interfere with or negate its destructive effect, resulting in antibiotic resistance. Known asDrug deliveryConditions treated with combination therapy includetuberculosis,leprosy,cancer,malaria, andHIV/AIDS. One major benefit of combination therapies is that they reduce development ofdrug resistance, since a pathogen or tumor is less likely to have resistance to multiple drugs simultaneously.Artemisinin-based monotherapies for malaria are explicitly discouraged to avoid the problem of developing resistance to the newer treatment. Drug Induced Blood Disorders causes of sickle cell anemia,pale skin non steroids antiinflammatory drugswhich causes ulcers Using drug repositioning, pharmaceutical companies have achieved a number successes, for examplePfizer'sViagrainerectile dysfunctionandCelgene'sthalidomidein severe erythema nodosum leprosum. Smaller companies, including Ore Pharmaceuticals,Biovista, Numedicus,Melior Discoveryand SOM Biotech are also performing drug repositioning on a systematic basis. These companies use a combination of approaches including in silico biology and in vivo/in vitro experimentation to assess a compound and develop and confirm hypotheses concerning its usage for new indications.

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Hematology Research

Lymphatic diseasesthis is a type of cancer of the lymphatic system. It can start almost any where in the body. It's believed to be caused by HIV, Epstein-Barr Syndrome, age and family history. Symptoms include weight loss, fever, swollen lymph nodes, night sweats, itchy skin, fatigue, chest pain, coughing and/or trouble swallowing. Thelymphatic systemis part of thecirculatory system, comprising a network oflymphatic vesselsthat carry a clear fluid called lymph directionally towards the heart. The lymphatic system was first described in the seventeenth century independently byOlaus RudbeckandThomas Bartholin. Unlike thecardiovascular systemthe lymphatic system is not a closed system. The human circulatory system processes an average of 20 litres ofbloodper day throughcapillary filtrationwhich removesplasmawhile leaving theblood cells. Roughly 17 litres of the filtered plasma get reabsorbed directly into the blood vessels, while the remaining 3 litres are left behind in theinterstitial fluid. One of the main functions of the lymph system is to provide an accessory return route to the blood for the surplus 3 litres. Lymphatic diseases are ofNon-Hodgkin's Lymphoma, Hodgkins. Thethymusis a specialized primarylymphoidorgan of theimmune system. Within the thymus,T cellsor Tlymphocytesmature. T cells are critical to theadaptive immune system, where the body adapts specifically to foreign invaders.One of the example of lymph node development. Formation oflymph nodeinto the tumor which lead to cancer called oncology.

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6thInternational Conference onCell&Stem Cell Research, Feb 29-March 02 2016, USA ; International Conference onInternal MedicineNovember 03-05, 2016 ,USA ; 4thInternational Conference onBlood Malignancies& Treatment April 18-20 2016,UAE; 3rdInternational conference onHematology&Blood DisordersNovember2-4 2015,USA ; International Conference onLeukemiaandBone marrow TransplantationNov 10-12 2016, Turkey ; 6thInternational Conference onHematologyandLymphNov 14-16, 2016;10thGlobal AnnualOncologists MeetingJuly 11-13 2016, Germany ;International Conference onInternal MedicineNovember 03-05, 2016,USA; 7thInternational conference onBiomarkers&Clinical ResearchNovember 28-30 2016,USA ; 8thEuro Global Summit onCancer TherapyNovember 03-05 2015,Spain; EMBLStem CellsConference 2016 Jun 3 - 5 2016,Germany ; 20thInternational Congress on Hematological Malignancies, March 18 20 2016,FL ; Conference onMyeloma& Lymphoma October 2015,New York ; ASH Meeting on Hematologic Malignancies Sep 17-19 2015,USA ; NCCN 10th Annual Congress: Hematologic Malignancies October 16 17 2015,USA;Congress of the International Society ofPaediatric OncologyOct 8-9 2015, South Africa;20th World Congress on Advances inOncology, October 8-10 2015,Greece; CombinationTherapies in CancerConference: Tools and Techniques for Developing Combinations More Efficiently Dec 06- 09 2015, UK

Various Aspects of Haematology

Pediatric Haematology and Oncologyis an internationalpeer-reviewedmedical journalthat covers all aspects ofpediatrichematologyandoncology. The journal covers immunology, pathology, and pharmacology in relation to blood diseases and cancer in children and shows how basic experimental research can contribute to the understanding of clinical problems. Physicians specialized in hematology are known ashematologistsorhaematologists. Their routine work mainly includes the care and treatment of patients with hematological diseases, although some may also work at the hematology laboratory viewingblood filmsandbone marrowslides under themicroscope, interpreting various hematological test results andblood clotting testresults. In some institutions, hematologists also manage the hematology laboratory. Physicians who work in hematology laboratories, and most commonly manage them, are pathologists specialized in the diagnosis of hematological diseases, referred to as hematopathologistsorhaematopathologists.Experimental Hematologyis apeer-reviewedmedical journalofhematology, which publishesoriginal researcharticles and reviews, as well as the abstracts of the annual proceedings of theSociety for Hematology and Stem Cells and they should be done under theHematology guidlines.

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Blood Based Products

Ablood substituteis a substance used to mimic and fulfill some functions ofbiologicalblood. It aims to provide an alternative toblood transfusion, which is transferring blood orblood-based productsfrom one person into another. Thus far, there are no well-acceptedoxygen-carryingblood substitutes, which is the typical objective of ared blood celltransfusion; however, there are widely available non-bloodvolume expandersfor cases where only volume restoration is required. These are helping doctors and surgeons avoid the risks of disease transmission and immune suppression, address the chronic blood donor shortage, and address the concerns of Jehovah's Witnesses and others who have religious objections to receiving transfused blood.Pathogen reductionusing riboflavin and UV lightis a method by which infectiouspathogensinblood for transfusionare inactivated by addingriboflavinand irradiating withUV light. This method reduces the infectious levels of disease-causing agents that may be found in donated blood components, while still maintaining good quality blood components for transfusion. This type of approach to increase blood safety is also known as pathogen inactivation in the industry. Anartificial cellorminimal cellis an engineered particle that mimics one or many functions of abiological cell. The term does not refer to a specific physical entity, but rather to the idea that certain functions or structures of biological cells can be replaced or supplemented with a synthetic entity. Often, artificial cells are biological or polymeric membranes which enclose biologically active materials. As such,nanoparticles,liposomes,polymersomes, microcapsules and a number of other particles have qualified as artificial cells.Manufacturing of semi synthetic products of drugs are known as therapeutic biological products.Anticoagulants(antithrombics) are a class of drugs that work to prevent thecoagulation(clotting) of blood. Such substances occur naturally in leeches and blood-sucking insects.

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Summary

Hematology is a branch of biology that includes various research areas such as pathology, internal medicine, clinical laboratory, physiology, immunology and pediatrics. This conference will witness a conglomeration of various arenas in Hematology and as it involves a vast range of medical streams within it, this conference will be an excellent platform for interdisciplinary interactions, to exchange and share knowledge under a single roof.

The organizing committee is gearing up for an exciting and informative conference program including plenary lectures, symposia, workshops on a variety of topics, poster presentations and various programs for participants from all over the world. We invite you to join us at the Hematology 2016, where you will be sure to have a meaningful experience with scholars from around the world.

For more details please visit: http://hematology.conferenceseries.com/

Importance & Scope:

Hematology 2016,Orlando, Florida, USAis expected to offer the best platform for the expertise, researchers, students and business delegates with its well organized scientific program covering every minute detail about hematology and blood diseases, from the basic causes behind blood diseases to the latest trends in diagnostic and treatment of blood diseases. This international event is an effort to find a weapon against chronic disorders like blood cancer, Sickle cell anemia, hemophilia, lymphoma and myeloma and to discuss the role of Immunoglobulin in blood, antibody and antigen reactions, the red blood cell and the immunological properties of blood which gives a better insight about the associated causes and disease portfolio.

Conferenceseries LLC welcomes all the hematologists, immunologists, pathologists, oncologists, research scholars, industrial professionals and student delegates from biomedical and healthcare sectors to be a part of the esteemed Hematology 2016. Advanced Diagnostic and therapeutic equipment along with the novel drugs for the blood diseases are an integral part of the Hematology research, hence it will be an excellent amalgamation of academia and industry as it involves every aspects of empirical and conceptual thinking in exploring new dimensions in this field. It is open to all types of research methodologies both from academia and industry.

Why Orlando?

Orlando is a city in the U.S. state of Florida, and the county seat of Orange County. Located in Central Florida, it is the center of the Orlando metropolitan area, which had a population of 2,134,411 at the 2010 census, making it the 26th largest metropolitan area in the United States, the sixth largest metropolitan area in the Southern United States, and the third largest metropolitan area in the state of Florida. In 2010, Orlando had a city-proper population of 238,300, making it the 77th largest city in the United States, the fifth largest city in Florida, and the states largest inland city.

The City of Orlando is nicknamed The City Beautiful and its symbol is the fountain at Lake Eola. Orlando is also known as The Theme Park Capital of the World and in 2014 its tourist attractions and events drew more than 62 million visitors. The Orlando International Airport (MCO) is the thirteenth busiest airport in the United States and the 29th busiest in the world. Buddy Dyer is Orlandos mayor. Orlandos famous attractions form the backbone of its tourism industry: Walt Disney World Resort, located approximately 21 miles (34 km) southwest of Downtown Orlando in Bay Lake, opened by the Walt Disney Company in 1971; the Universal Orlando Resort, opened in 1999 as a major expansion of Universal Studios Florida; SeaWorld; Gatorland; and Wet n Wild. With the exception of Walt Disney World, most major attractions are located along International Drive. The city is also one of the busiest American cities for conferences and conventions.

Conference Highlights

A Unique Opportunity for Advertisers and Sponsors at this International event

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Associations in USA

Associations Worldwide

Universities in USA

Universities Worldwide

Companies in USA

Hospitals in USA

Hospitals in Worldwide

Glance at Market of Hematology

According to market study, market value of Hematology at present is $15.13 billion. A major part of research is going on at the top Universities across the globe, the grants allotted for this research field is around $10.54 billion. Many companies are associated with the blood testing equipment along with various diagnostic instruments, hematologic drugs and other therapeutics, the revenue generated is around $21.1 billion on average by this companies. Besides this various societies and research labs are also associated in this research field. More than 40% research work on Hematology is going on in USA, as around 176 Universities in USA are working in this field, along with 24 Societies, besides that there are almost 40 companies in USA which deals with diagnostic and testing equipment. Market value of Hematology at present in USA is $3.13 billion at present, university grants allotted by government is about $2.10 billion and average revenue generated by the industries in USA is $8.1billion. The global hematology market is divided into hematology products& hematology services. The hematology products segment holds the largest share of the hematology market in 2016. It is also expected to grow at the highest growth rate by next five years, owing to the increasing development of new hematology reagents. In addition, based on the end-users, the global hematology market has been segmented into commercial organizations, stand-alone hospitals, research institutes, and clinical testing labs. The clinical testing labs hold the largest share of the hematology market in 2016.

"3rd International Conference on Hematology & Blood Disorders" organized by OMICS Group International was successfully held at Double Tree by Hilton Hotel Atlanta Airport at Atlanta, USA during November 02-04, 2015. The conference was organized around the theme Research strategies, advanced technologies and upcoming challenges in Hematology."

The conference was marked with the presence of renowned scientists, talented young researchers, students and business delegates representing more than 25 different countries ultimately driving the event into the path of success.

OMICS Group International would like to convey a warm gratitude to all the honorable guests of Hematology-2015, Robert H Schiestl University of California, USA; C Cameron Yin University of Texas, USA; Dianzheng Zhang, Philadelphia College of Osteopathic Medicine, USA;Jay S Raval, University of North Carolina, USA and Robert Michael Davidson The American Institute of Stress, USA

The highlights of the conference were its educative and effectual keynote lectures by:

Robert H Schiestl, University of California, USA

C Cameron Yin , University of Texas, USA

Knox Van Dyke, West Virginia University, USA

Knox Van Dyke,West Virginia University, USA

Robert Michael Davidson , The American Institute of Stress, USA

OMICS Group also took the privilege of felicitating Hematology-2015 Organizing Committee, Editorial Board Members and Keynote Speakers whose support led the conference into the path of excellence. Our special gratitude to our media partnersAll Congress,Business Vibes,Clocate, Medical News Today,Oncology Education and ORIC Publications.

Hematology-2014

"2ndInternational Conference on Hematology & Blood Disorders" organized by OMICS Group International was successfully held at Double Tree by Hilton Hotel BWI Airport at Baltimore, USA during September 29- October 01, 2014. The conference was organized around the themeOn the Path of Identifying Novel Therapeutics for Blood Disorders."

OMICS Group International would like to convey a warm gratitude to all the honorable guests of Hematology-2014, Mark Roschewski, National Institutes of Health, USA; E. Brad Thompson, University of Houston, USA; Britt Gustafsson, Center for Allogeneic Stem Cell Transplantation, Sweden; Effie Liakopoulou, Genimbi Inc, USA and Ping Xie, Rutgers University, USA

The highlights of the conference were its educative and effectual keynote lectures by:

OMICS Group also took the privilege of felicitating Hematology-2014 Organizing Committee, Editorial Board Members and Keynote Speakers whose support led the conference into the path of excellence. Our special gratitude to our exhibitorOne Lambda, USA and media partnersAll Congress,Business Vibes,Clocate, Medical News Today,Oncology Education and ORIC Publications.

Hematology-2013

The highlights of the conference were its educative and effectual keynote lectures by:

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Hematology Conferences | Blood Disorder Conferences | USA ...

Induced Pluripotent Stem Cells: 10 Years After the …

By adminSeptember 28, 2016Induced Pluripotent Stem Cells

Human cortex grown in a petri dish. Eye diseases treated with retinal cells derived from a patients own skin cells. New drugs tested on human cells instead of animal models.

Research and emerging treatments with stem cells today can be traced to a startling discovery 10 years ago when Shinya Yamanaka, M.D., Ph.D., and his graduate student Kazutoshi Takahashi, Ph.D., reported a way to reprogram adult mouse cells and coax them back to their embryonic state pluripotent stem cells.

A year later, they accomplished the feat with human cells. For this research coup and his leading role pioneering stem cell work, Yamanaka who holds academic appointments at Kyoto University and UC San Francisco was the co-recipient of the 2012 Nobel Prize in Medicine or Physiology.

The breakthrough provides a limitless supply of induced pluripotent stem cells (iPSCs) that can then be directed down any developmental path to generate specific types of adult cells, from skin to heart to neuron, for use in basic research, drug discovery and treating disease.

The achievement opened up a practical way and in some critical cases, the only way to directly study human diseases in a dish, and track the early stages of both healthy and abnormal development. It also allowed researchers to screen new drugs directly in human cells rather than relying on animal models, which more often than not fail to accurately predict a new drugs effects on people.

The dazzling iPSC breakthrough has spurred rapid progress in some areas and posed major challenges in others. It has already proved a boon to basic research, but applying the new technology to treat diseases remains daunting. Some types of cells have proved difficult to reprogram, and even the protocols for doing so are still in flux as this is still a very young field.

For many basic biomedical scientists, the capability offered by iPSCs technology is like a dream come true, says neuroscientist Arnold Kriegstein, M.D., Ph.D., director of UCSFs Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research.

Induced pluripotent stem cells have given us a window into human development unlike anything we had before, Kriegstein said. Im interested in the early development of the brains cortex. Of course, weve never had unrestricted access to living human brain cells. Now we can take skin cells and grow human cortex in a dish. Its a game-changer for discovery about early human development.

Kriegstein is enthusiastic about what researchers can learn from organoids a pea-sized stage of a developing organ derived from iPSCs. By this stage, cells are already clumping together and starting to signal and differentiate into what will become the adult organ.

Its a very close model of the real thing, Kriegstein says. We have recently discovered that even in this early stage, the organoids are able to develop intrinsic organization, including a front-and-back orientation, and different parts start to look like they do in the embryonic brain.

Some scientific papers have suggested that organoids can model diseases found in adulthood even disorders of late adulthood such as Alzheimers disease.

Even though organoids can reveal developmental steps not seen before, Kriegstein worries that some researchers are getting too far ahead of themselves.

Its an embryonic brain, he stresses. The longest period of growth we can model would be full fetal development. How likely is it that gene expression, cell signaling and a myriad of other interactions at this organoid stage could accurately represent the development of Alzheimers disease, a disease that affects people at 60 or 70?

I think we need to take some of these studies with a grain of salt. Stem cell technology now is so variable that replication is difficult. We need to establish protocols to reliably compare different methods and then use these standardized methodologies to advance research and treatment. But I am 100 percent convinced that we will get there.

Yamanaka currently directs the 500-person Center for iPS Cell Research and Application at Kyoto University, runs a research lab at the Gladstone Institute for Cardiovascular Disease in San Francisco, and serves as a professor of anatomy at UCSF, and Takahashi is a visiting scientist at the Gladstone Institutes and runs Yamanakas lab there. Both have continued to build on their iPSC work, as have other researchers.

In their seminal work, Yamanaka and Takahashi had introduced four genetic factors to prompt adult cells back to the pluripotent state. Soon after their iPSC breakthrough, Sheng Ding, Ph.D., who has a lab at the Gladstone Institutes and is a professor in UCSF's Department of Pharmaceutical Chemistry, began refining the reprogramming cocktail.

Eventually, Ding was able to substitute drug-like molecules for these gene transcription factors, eliminating the risk of new genetic material altering the cells. Today, labs around the world pursue and tout different chemical recipes, often depending on the type of cell they are trying to reprogram.

Other recent advances to induce pluripotency harness different kinds of proteins that influence gene activity in the cell nucleus. Robert Blelloch, M.D., Ph.D., a stem cell scientist at UCSFs Broad Center, has shown that some small RNA molecules called microRNAs promote adult cell de-differentiation and others promote the reverse: ability of stem cells to differentiate into adult cells. By tweaking microRNA activity, his lab has been able to improve reprogramming yields a hundred-fold.

He and colleagues have also become intrigued by the role of so-called epigenetic factors naturally occurring or introduced molecules that modify proteins in the nucleus. Manipulation of these molecules too can affect the efficiency of inducing pluripotent cells.

Six years after Yamanakas iPSCs discovery, researchers in a very different field developed a new gene-editing technology of unprecedented speed and precision, known as CRISPR-Cas9. The potent new tool has revolutionized efforts to cut and paste genes and has been very quickly adopted by thousands of researchers in basic biology and drug development.

CRISPR has provided us with an extraordinary new capability, Kriegstein says. It allows us to tease apart the genetic causes or contributors to developmental diseases. We can edit out mutations to determine if they are critical to early developmental defects.

CRISPRs speed and precision may some day allow stem cell researchers to reach their most ambitious goal: Genetically abnormal cells from patients with inherited diseases such as sickle cell anemia or Huntingtons could be reprogrammed to the pluripotent stem cell state; their genetic defects could be edited in a petri dish before being differentiated into healthy adult cells. These cells could then be transplanted into patients to restore normal function.

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Induced Pluripotent Stem Cells: 10 Years After the ...

Stem Cell Basics V. | stemcells.nih.gov

By adminSeptember 27, 2016Adult Stem Cells

Human embryonic and adult stem cells each have advantages and disadvantages regarding potential use for cell-based regenerative therapies. One major difference between adult and embryonic stem cells is their different abilities in the number and type of differentiated cell types they can become. Embryonic stem cells can become all cell types of the body because they are pluripotent. Adult stem cells are thought to be limited to differentiating into different cell types of their tissue of origin.

Embryonic stem cells can be grown relatively easily in culture. Adult stem cells are rare in mature tissues, so isolating these cells from an adult tissue is challenging, and methods to expand their numbers in cell culture have not yet been worked out. This is an important distinction, as large numbers of cells are needed for stem cell replacement therapies.

Scientists believe that tissues derived from embryonic and adult stem cells may differ in the likelihood of being rejected after transplantation. We don't yet know for certainwhether tissues derived from embryonic stem cells would cause transplant rejection, since relatively few clinical trialshave testedthe safety of transplanted cells derived from hESCS.

Adult stem cells, and tissues derived from them, are currently believed less likely to initiate rejection after transplantation. This is because a patient's own cells could be expanded in culture, coaxed into assuming a specific cell type (differentiation), and then reintroduced into the patient. The use of adult stem cells and tissues derived from the patient's own adult stem cells would mean that the cells are less likely to be rejected by the immune system. This represents a significant advantage, as immune rejection can be circumvented only by continuous administration of immunosuppressive drugs, and the drugs themselves may cause deleterious side effects.

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Stem Cell Basics V. | stemcells.nih.gov

Stem Cell Doctors | Stem Cell Therapy | Tijuana, Mexico

By adminSeptember 24, 2016Stem Cell Doctors

Treatment Plans

We believe the key to the most effective stem cell treatment is through treatment plan customization. Stem Cell Doctorsoffers access to individualized stem cell treatment plans.

Stem Cell Doctorsoffers patients access to cutting-edge stem cell therapy. We have partnered with some of the top stem cell innovators in the countryto develop the best treatments.

With years of experience, our stem cell doctors are not only very active in the treatment of our patients but are also pioneers in the stem cell researchand medical biotech fields.

The Stem Cell treatment performed at our clinics is a painless medical procedure where Stem Cells (cellular building blocks) are usually administered intravenously.

Following the treatment, the Stem Cells will travel throughout the body, detecting damaged cells and tissue and attempts to restore them. The Stem Cells can also stimulate existing normal cells and tissues to operate at a higher level of function, boosting the bodys own repair mechanisms to aid in the healing process.

These highly adaptive cells then remain in the body, continually locating and repairing any damage they encounter.

Dr Cesar Amescua, is a board-certified anesthesiologist and pain management specialistwith extensive experience in the field of stem cell therapy. Dr. Amescuaalso trains physicians in the evaluation and treatment of patients receiving stem cell therapy.

Dr. Cesar Amescua is the Medical Director of Hospital Angeles Tijuana, where hetreats a wide range of chronic pain conditions such as low back pain and neck pain, neuropathic pain, spinal cord stimulation, osteoporosis, persistent post-operative pain and complex regional pain syndrome (known before as reflex sympathetic dystrophy, uncommon form of intense chronic pain, failed back surgery syndrome and cancer pain.

Dr. Cesar Amescua personally provides assurance of the high level of service that our patients require. From diagnosis to treatment to recovery Dr. Amescuas professional, caring approach brings a significant added benefit for both patients and families.

Stem cells are the basic building blocks of life, the basic cells from which our bodies are made. They are formed at conception and specialized to become all the different tissues of the body: muscle, nerve, organs, bone, blood and so on. In general terms, stem cells are progenitor cells that lead the creation of new cells. They are regenerative in their function; they are regenerative cells.

We tap into our bodys stem cell reserve to repair and replace injured or diseased tissue. Unfortunately, our reserve is limited and as it becomes depleted, the regenerative power of our body decreases and we succumb to diseases, disorders and the ravages and ramifications of aging.

There are three sources of stem cells from a patients body that can be used clinically; these are bone marrow, peripheral blood and fat (adipose tissue).

Researchers are testing adult stem cells to treat other conditions, including a number of degenerative diseases such as heart failure.

The best source to harvest stem cells from ones body is the FAT also known as Adipose Tissue. It is rich in mesenchymal stem cells and 100x more stem cells can be harvested from fat as compared to bone marrow for example.

Essentially, stem cells are progenitor cells which are capable of regeneration and differentiation morphing into a wide range of specialized cell types. Once administered, stem cells follow inflammatory signals from damaged tissues and have multiple ways of repairing these damaged areas.

We have treated a very large number of patients with multiple diseases our clinical experience is unsurpassed.

We always use cells sourced from the patient. And in genetic cases we can use cells from a matched relative.

Stem Cell Doctorsoffers the highest level of patient care, working hard to provide a worry free process for you.

We are always striving to utilize the best technology and the newest advances in order to improve the outcomes

After several promising treatments in Panama using stem cell technology...

Scientists have identified a new way to treat disorders of the brain using stem...

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Stem Cell Doctors | Stem Cell Therapy | Tijuana, Mexico

The Promise of Induced Pluripotent Stem Cells (iPSCs …

By adminSeptember 23, 2016Induced Pluripotent Stem Cells

Charles A. Goldthwaite, Jr., Ph.D.

In 2006, researchers at Kyoto University in Japan identified conditions that would allow specialized adult cells to be genetically "reprogrammed" to assume a stem cell-like state. These adult cells, called induced pluripotent stem cells (iPSCs), were reprogrammed to an embryonic stem cell-like state by introducing genes important for maintaining the essential properties of embryonic stem cells (ESCs). Since this initial discovery, researchers have rapidly improved the techniques to generate iPSCs, creating a powerful new way to "de-differentiate" cells whose developmental fates had been previously assumed to be determined.

Although much additional research is needed, investigators are beginning to focus on the potential utility of iPSCs as a tool for drug development, modeling of disease, and transplantation medicine. The idea that a patient's tissues could provide him/ her a copious, immune-matched supply of pluripotent cells has captured the imagination of researchers and clinicians worldwide. Furthermore, ethical issues associated with the production of ESCs do not apply to iPSCs, which offer a non-controversial strategy to generate patient-specific stem cell lines. As an introduction to this exciting new field of stem cell research, this chapter will review the characteristics of iPSCs, the technical challenges that must be overcome before this strategy can be deployed, and the cells' potential applications to regenerative medicine.

As noted in other chapters, stem cells represent a precious commodity. Although present in embryonic and adult tissues, practical considerations such as obtaining embryonic tissues and isolating relatively rare cell types have limited the large-scale production of populations of pure stem cells (see the Chapter, "Alternate Methods for Preparing Pluripotent Stem Cells" for details). As such, the logistical challenges of isolating, culturing, purifying, and differentiating stem cell lines that are extracted from tissues have led researchers to explore options for "creating" pluripotent cells using existing non-pluripotent cells. Coaxing abundant, readily available differentiated cells to pluripotency would in principle eliminate the search for rare cells while providing the opportunity to culture clinically useful quantities of stem-like cells.

One strategy to accomplish this goal is nuclear reprogramming, a technique that involves experimentally inducing a stable change in the nucleus of a mature cell that can then be maintained and replicated as the cell divides through mitosis. These changes are most frequently associated with the reacquisition of a pluripotent state, thereby endowing the cell with developmental potential. The strategy has historically been carried out using techniques such as somatic cell nuclear transfer (SCNT),1,2 altered nuclear transfer (ANT),3,4 and methods to fuse somatic cells with ESCs5,6 (see "Alternate Methods for Preparing Pluripotent Stem Cells" for details of these approaches). From a clinical perspective, these methods feature several drawbacks, such as the creation of an embryo or the development of hybrid cells that are not viable to treat disease. However, in 2006, these efforts informed the development of nuclear reprogramming in vitro, the breakthrough method that creates iPSCs.

This approach involves taking mature "somatic" cells from an adult and introducing the genes that encode critical transcription factor proteins, which themselves regulate the function of other genes important for early steps in embryonic development (See Fig. 10.1). In the initial 2006 study, it was reported that only four transcription factors (Oct4, Sox2, Klf4, and c-Myc) were required to reprogram mouse fibroblasts (cells found in the skin and other connective tissue) to an embryonic stem celllike state by forcing them to express genes important for maintaining the defining properties of ESCs.7 These factors were chosen because they were known to be involved in the maintenance of pluripotency, which is the capability to generate all other cell types of the body. The newly-created iPSCs were found to be highly similar to ESCs and could be established after several weeks in culture.7,8 In 2007, two different research groups reached a new milestone by deriving iPSCs from human cells, using either the original four genes9 or a different combination containing Oct4, Sox2, Nanog, and Lin28.10 Since then, researchers have reported generating iPSCs from somatic tissues of the monkey11 and rat.12,13

However, these original methods of reprogramming are inefficient, yielding iPSCs in less than 1% of the starting adult cells.14,15 The type of adult cell used also affects efficiency; fibroblasts require more time for factor expression and have lower efficiency of reprogramming than do human keratinocytes, mouse liver and stomach cells, or mouse neural stem cells.1419

Several approaches have been investigated to improve reprogramming efficiency and decrease potentially detrimental side effects of the reprogramming process. Since the retroviruses used to deliver the four transcription factors in the earliest studies can potentially cause mutagenesis (see below), researchers have investigated whether all four factors are absolutely necessary. In particular, the gene c-Myc is known to promote tumor growth in some cases, which would negatively affect iPSC usefulness in transplantation therapies. To this end, researchers tested a three-factor approach that uses the orphan nuclear receptor Esrrb with Oct4 and Sox2, and were able to convert mouse embryonic fibroblasts to iPSCs.20 This achievement corroborates other reports that c-Myc is dispensable for direct reprogramming of mouse fibroblasts.21 Subsequent studies have further reduced the number of genes required for reprogramming,2226 and researchers continue to identify chemicals that can either substitute for or enhance the efficiency of transcription factors in this process.27 These breakthroughs continue to inform and to simplify the reprogramming process, thereby advancing the field toward the generation of patient-specific stem cells for clinical application. However, as the next section will discuss, the method by which transcription factors are delivered to the somatic cells is critical to their potential use in the clinic.

Figure 10.1. Generating Induced Pluripotent Stem Cells (iPSCs).

2008 Terese Winslow

Reprogramming poses several challenges for researchers who hope to apply it to regenerative medicine. To deliver the desired transcription factors, the DNA that encodes their production must be introduced and integrated into the genome of the somatic cells. Early efforts to generate iPSCs accomplished this goal using retroviral vectors. A retrovirus is an RNA virus that uses an enzyme, reverse transcriptase, to replicate in a host cell and subsequently produce DNA from its RNA genome. This DNA incorporates into the host's genome, allowing the virus to replicate as part of the host cell's DNA. However, the forced expression of these genes cannot be controlled fully, leading to unpredictable effects.28 While other types of integrating viruses, such as lentiviruses, can increase the efficiency of reprogramming,16 the expression of viral transgenes remains a critical clinical issue. Given the dual needs of reducing the drawbacks of viral integration and maximizing reprogramming efficiency, researchers are exploring a number of strategies to reprogram cells in the absence of integrating viral vectors2730 or to use potentially more efficient integrative approaches.31,32

Before reprogramming can be considered for use as a clinical tool, the efficiency of the process must improve substantially. Although researchers have begun to identify the myriad molecular pathways that are implicated in reprogramming somatic cells,15 much more basic research will be required to identify the full spectrum of events that enable this process. Simply adding transcription factors to a population of differentiated cells does not guarantee reprogrammingthe low efficiency of reprogramming in vitro suggests that additional rare events are necessary to generate iPSCs, and the efficiency of reprogramming decreases even further with fibroblasts that have been cultured for long time periods.33 Furthermore, the differentiation stage of the starting cell appears to impact directly the reprogramming efficiency; mouse hematopoietic stem and progenitor cells give rise to iPSCs up to 300 times more efficiently than do their terminally-differentiated B- and T-cell counterparts.34 As this field continues to develop, researchers are exploring the reprogramming of stem or adult progenitor cells from mice24,25,34,35 and humans23,26 as one strategy to increase efficiency compared to that observed with mature cells.

As these discussions suggest, clinical application of iPSCs will require safe and highly efficient generation of stem cells. As scientists increase their understanding of the molecular mechanisms that underlie reprogramming, they will be able to identify the cell types and conditions that most effectively enable the process and use this information to design tools for widespread use. Clinical application of these cells will require methods to reprogram cells while minimizing DNA alterations. To this end, researchers have found ways to introduce combinations of factors in a single viral "cassette" into a known genetic location.36 Evolving tools such as these will enable researchers to induce programming more safely, thereby informing basic iPSC research and moving this technology closer to clinical application.

ESCs and iPSCs are created using different strategies and conditions, leading researchers to ask whether the cell types are truly equivalent. To assess this issue, investigators have begun extensive comparisons to determine pluripotency, gene expression, and function of differentiated cell derivatives. Ultimately, the two cell types exhibit some differences, yet they are remarkably similar in many key aspects that could impact their application to regenerative medicine. Future experiments will determine the clinical significance (if any) of the observed differences between the cell types.

Other than their derivation from adult tissues, iPSCs meet the defining criteria for ESCs. Mouse and human iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cell types from all three primitive embryonic layers, and displaying the capacity to contribute to many different tissues when injected into mouse embryos at a very early stage of development. Initially, it was unclear that iPSCs were truly pluripotent, as early iPSC lines contributed to mouse embryonic development but failed to produce live-born progeny as do ESCs. In late 2009, however, several research groups reported mouse iPSC lines that are capable of producing live births,37,38 noting that the cells maintain a pluripotent potential that is "very close to" that of ESCs.38 Therefore, iPSCs appear to be truly pluripotent, although they are less efficient than ESCs with respect to differentiating into all cell types.38 In addition, the two cell types appear to have similar defense mechanisms to thwart the production of DNA-damaging reactive oxygen species, thereby conferring the cells with comparable capabilities to maintain genomic integrity.39

Undifferentiated iPSCs appear molecularly indistinguishable from ESCs. However, comparative genomic analyses reveal differences between the two cell types. For example, hundreds of genes are differentially expressed in ESCs and iPSCs,40 and there appear to be subtle but detectable differences in epigenetic methylation between the two cell types.41,42 Genomic differences are to be expected; it has been reported that gene-expression profiles of iPSCs and ESCs from the same species differ no more than observed variability among individual ESC lines.43 It should be noted that the functional implications of these findings are presently unknown, and observed differences may ultimately prove functionally inconsequential.44

Recently, some of the researchers who first generated human iPSCs compared the ability of iPSCs and human ESCs to differentiate into neural cells (e.g., neurons and glia).45 Their results demonstrated that both cell types follow the same steps and time course during differentiation. However, although human ESCs differentiate into neural cells with a similar efficiency regardless of the cell line used, iPSC-derived neural cells demonstrate lower efficiency and greater variability when differentiating into neural cells. These observations occurred regardless of which of several iPSC-generation protocols were used to reprogram the original cell to the pluripotent state. Experimental evidence suggests that individual iPSC lines may be "epigenetically unique" and predisposed to generate cells of a particular lineage. However, the authors believe that improvements to the culturing techniques may be able to overcome the variability and inefficiency described in this report.

These findings underpin the importance of understanding the inherent variability among discrete cell populations, whether they are iPSCs or ESCs. Characterizing the variability among iPSC lines will be crucial to apply the cells clinically. Indeed, the factors that make each iPSC line unique may also delay the cells' widespread use, as differences among the cell lines will affect comparisons and potentially influence their clinical behavior. For example, successfully modeling disease requires being able to identify the cellular differences between patients and controls that lead to dysfunction. These differences must be framed in the context of the biologic variability inherent in a given patient population. If iPSC lines are to be used to model disease or screen candidate drugs, then variability among lines must be minimized and characterized fully so that researchers can understand how their observed results match to the biology of the disease being studied. As such, standardized assays and methods will become increasingly important for the clinical application of iPSCs, and controls must be developed that account for variability among the iPSCs and their derivatives.

Additionally, researchers must understand the factors that initiate reprogramming towards pluripotency in different cell types. A recent report has identified one factor that initiates reprogramming in human fibroblasts,46 setting the groundwork for developing predictive models to identify those cells that will become iPSCs. An iPSC may carry a genetic "memory" of the cell type that it once was, and this "memory" will likely influence its ability to be reprogrammed. Understanding how this memory varies among different cell types and tissues will be necessary to reprogram successfully.

iPSCs have the potential to become multipurpose research and clinical tools to understand and model diseases, develop and screen candidate drugs, and deliver cell-replacement therapy to support regenerative medicine. This section will explore the possibilities and the challenges that accompany these medical applications, with the caveat that some uses are more immediate than others. For example, researchers currently use stem cells to test/screen drugs or as study material to identify molecules or genes implicated in regeneration. Conducting experiments or testing candidate drugs on human cells grown in culture enables researchers to understand fundamental principles and relationships that will ultimately inform the use of stem cells as a source of tissue for transplantation. Therefore, using iPSCs in cell-replacement therapies is a future application of these cells, albeit one that has tremendous clinical potential. The following discussion will highlight recent efforts toward this goal while recognizing the challenges that must be overcome for these cells to reach the clinic.

Reprogramming technology offers the potential to treat many diseases, including Alzheimer's disease, Parkinson's disease, cardiovascular disease, diabetes, and amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig's disease). In theory, easily-accessible cell types (such as skin fibroblasts) could be biopsied from a patient and reprogrammed, effectively recapitulating the patient's disease in a culture dish. Such cells could then serve as the basis for autologous cell replacement therapy. Because the source cells originate within the patient, immune rejection of the differentiated derivatives would be minimized. As a result, the need for immunosuppressive drugs to accompany the cell transplant would be lessened and perhaps eliminated altogether. In addition, the reprogrammed cells could be directed to produce the cell types that are compromised or destroyed by the disease in question. A recent experiment has demonstrated the proof of principle in this regard,47 as iPSCs derived from a patient with ALS were directed to differentiate into motor neurons, which are the cells that are destroyed in the disease.

Although much additional basic research will be required before iPSCs can be applied in the clinic, these cells represent multi-purpose tools for medical research. Using the techniques described in this article, researchers are now generating myriad disease-specific iPSCs. For example, dermal fibroblasts and bone marrow-derived mesencyhmal cells have been used to establish iPSCs from patients with a variety of diseases, including ALS, adenosine deaminase deficiency-related severe combined immunodeficiency, Shwachman- Bodian-Diamond syndrome, Gaucher disease type III, Duchenne and Becker muscular dystrophies, Parkinson's disease, Huntington's disease, type 1 diabetes mellitus, Down syndrome/trisomy 21, and spinal muscular atrophy.4749 iPSCs created from patients diagnosed with a specific genetically-inherited disease can then be used to model disease pathology. For example, iPSCs created from skin fibroblasts taken from a child with spinal muscular atrophy were used to generate motor neurons that showed selective deficits compared to those derived from the child's unaffected mother.48 As iPSCs illuminate the development of normal and disease-specific pathologic tissues, it is expected that discoveries made using these cells will inform future drug development or other therapeutic interventions.

One particularly appealing aspect of iPSCs is that, in theory, they can be directed to differentiate into a specified lineage that will support treatment or tissue regeneration. Thus, somatic cells from a patient with cardiovascular disease could be used to generate iPSCs that could then be directed to give rise to functional adult cardiac muscle cells (cardiomyocytes) that replace diseased heart tissue, and so forth. Yet while iPSCs have great potential as sources of adult mature cells, much remains to be learned about the processes by which these cells differentiate. For example, iPSCs created from human50 and murine fibroblasts5153 can give rise to functional cardiomyocytes that display hallmark cardiac action potentials. However, the maturation process into cardiomyocytes is impaired when iPSCs are usedcardiac development of iPSCs is delayed compared to that seen with cardiomyocytes derived from ESCs or fetal tissue. Furthermore, variation exists in the expression of genetic markers in the iPSC-derived cardiac cells as compared to that seen in ESC-derived cardiomyocytes. Therefore, iPSC-derived cardiomyocytes demonstrate normal commitment but impaired maturation, and it is unclear whether observed defects are due to technical (e.g., incomplete reprogramming of iPSCs) or biological barriers (e.g., functional impairment due to genetic factors). Thus, before these cells can be used for therapy, it will be critical to distinguish between iPSC-specific and disease-specific phenotypes.

However, it must be noted that this emerging field is continually evolving; additional basic iPSC research will be required in parallel with the development of disease models. Although the reprogramming technology that creates iPSCs is currently imperfect, these cells will likely impact future therapy, and "imperfect" cells can illuminate many areas related to regenerative medicine. However, iPSC-derived cells that will be used for therapy will require extensive characterization relative to what is sufficient to support disease modeling studies. To this end, researchers have begun to use imaging techniques to observe cells that are undergoing reprogramming to distinguish true iPSCs from partially-reprogrammed cells.54 The potential for tumor formation must also be addressed fully before any iPSC derivatives can be considered for applied cell therapy. Furthermore, in proposed autologous therapy applications, somatic DNA mutations (e.g., non-inherited mutations that have accumulated during the person's lifetime) retained in the iPSCs and their derivatives could potentially impact downstream cellular function or promote tumor formation (an issue that may possibly be circumvented by creating iPSCs from a "youthful" cell source such as umbilical cord blood).55 Whether these issues will prove consequential when weighed against the cells' therapeutic potential remains to be determined. While the promise of iPSCs is great, the current levels of understanding of the cells' biology, variability, and utility must also increase greatly before iPSCs become standard tools for regenerative medicine.

Since their discovery four years ago, induced pluripotent stem cells have captured the imagination of researchers and clinicians seeking to develop patient-specific therapies. Reprogramming adult tissues to embryonic-like states has countless prospective applications to regenerative medicine, drug development, and basic research on stem cells and developmental processes. To this point, a PubMed search conducted in April 2010 using the term "induced pluripotent stem cells" (which was coined in 2006) returned more than 1400 publications, indicating a highly active and rapidlydeveloping research field.

However, many technical and basic science issues remain before the promise offered by iPSC technology can be realized fully. For putative regenerative medicine applications, patient safety is the foremost consideration. Standardized methods must be developed to characterize iPSCs and their derivatives. Furthermore, reprogramming has demonstrated a proof of-principle, yet the process is currently too inefficient for routine clinical application. Thus, unraveling the molecular mechanisms that govern reprogramming is a critical first step toward standardizing protocols. A grasp on the molecular underpinnings of the process will shed light on the differences between iPSCs and ESCs (and determine whether these differences are clinically significant). Moreover, as researchers delve more deeply into this field, the effects of donor cell populations can be compared to support a given application; i.e., do muscle-derived iPSCs produce more muscle than skin-derived cells? Based on the exciting developments in this area to date, induced pluripotent stem cells will likely support future therapeutic interventions, either directly or as research tools to establish novel models for degenerative disease that will inform drug development. While much remains to be learned in the field of iPSC research, the development of reprogramming techniques represents a breakthrough that will ultimately open many new avenues of research and therapy.

Chapter 9|Table of Contents|Chapter 11

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