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Hematopoietic stem cell transplantation – Wikipedia

Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood.[1][2] It may be autologous (the patient's own stem cells are used), allogeneic (the stem cells come from a donor) or syngeneic (from an identical twin).[1][2] It is a medical procedure in the field of hematology, most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma or leukemia.[2] In these cases, the recipient's immune system is usually destroyed with radiation or chemotherapy before the transplantation. Infection and graft-versus-host disease are major complications of allogeneic HSCT.[2]

Hematopoietic stem cell transplantation remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases. As survival following the procedure has increased, its use has expanded beyond cancer, such as autoimmune diseases.[3][4]

Indications for stem cell transplantation are as follows:

Many recipients of HSCTs are multiple myeloma[5] or leukemia patients[6] who would not benefit from prolonged treatment with, or are already resistant to, chemotherapy. Candidates for HSCTs include pediatric cases where the patient has an inborn defect such as severe combined immunodeficiency or congenital neutropenia with defective stem cells, and also children or adults with aplastic anemia[7] who have lost their stem cells after birth. Other conditions[8] treated with stem cell transplants include sickle-cell disease, myelodysplastic syndrome, neuroblastoma, lymphoma, Ewing's sarcoma, desmoplastic small round cell tumor, chronic granulomatous disease and Hodgkin's disease. More recently non-myeloablative, "mini transplant(microtransplantation)," procedures have been developed that require smaller doses of preparative chemo and radiation. This has allowed HSCT to be conducted in the elderly and other patients who would otherwise be considered too weak to withstand a conventional treatment regimen.

In 2006 a total of 50,417 first hematopoietic stem cell transplants were reported as taking place worldwide, according to a global survey of 1327 centers in 71 countries conducted by the Worldwide Network for Blood and Marrow Transplantation. Of these, 28,901 (57 percent) were autologous and 21,516 (43 percent) were allogeneic (11,928 from family donors and 9,588 from unrelated donors). The main indications for transplant were lymphoproliferative disorders (54.5 percent) and leukemias (33.8 percent), and the majority took place in either Europe (48 percent) or the Americas (36 percent).[9]

In 2014, according to the World Marrow Donor Association, stem cell products provided for unrelated transplantation worldwide had increased to 20,604 (4,149 bone marrow donations, 12,506 peripheral blood stem cell donations, and 3,949 cord blood units).[10]

Autologous HSCT requires the extraction (apheresis) of haematopoietic stem cells (HSC) from the patient and storage of the harvested cells in a freezer. The patient is then treated with high-dose chemotherapy with or without radiotherapy with the intention of eradicating the patient's malignant cell population at the cost of partial or complete bone marrow ablation (destruction of patient's bone marrow's ability to grow new blood cells). The patient's own stored stem cells are then transfused into his/her bloodstream, where they replace destroyed tissue and resume the patient's normal blood cell production. Autologous transplants have the advantage of lower risk of infection during the immune-compromised portion of the treatment since the recovery of immune function is rapid. Also, the incidence of patients experiencing rejection (and graft-versus-host disease is impossible) is very rare due to the donor and recipient being the same individual. These advantages have established autologous HSCT as one of the standard second-line treatments for such diseases as lymphoma.[11]

However, for other cancers such as acute myeloid leukemia, the reduced mortality of the autogenous relative to allogeneic HSCT may be outweighed by an increased likelihood of cancer relapse and related mortality, and therefore the allogeneic treatment may be preferred for those conditions.[12] Researchers have conducted small studies using non-myeloablative hematopoietic stem cell transplantation as a possible treatment for type I (insulin dependent) diabetes in children and adults. Results have been promising; however, as of 2009[update] it was premature to speculate whether these experiments will lead to effective treatments for diabetes.[13]

Allogeneics HSCT involves two people: the (healthy) donor and the (patient) recipient. Allogeneic HSC donors must have a tissue (HLA) type that matches the recipient. Matching is performed on the basis of variability at three or more loci of the HLA gene, and a perfect match at these loci is preferred. Even if there is a good match at these critical alleles, the recipient will require immunosuppressive medications to mitigate graft-versus-host disease. Allogeneic transplant donors may be related (usually a closely HLA matched sibling), syngeneic (a monozygotic or 'identical' twin of the patient - necessarily extremely rare since few patients have an identical twin, but offering a source of perfectly HLA matched stem cells) or unrelated (donor who is not related and found to have very close degree of HLA matching). Unrelated donors may be found through a registry of bone marrow donors such as the National Marrow Donor Program. People who would like to be tested for a specific family member or friend without joining any of the bone marrow registry data banks may contact a private HLA testing laboratory and be tested with a mouth swab to see if they are a potential match.[14] A "savior sibling" may be intentionally selected by preimplantation genetic diagnosis in order to match a child both regarding HLA type and being free of any obvious inheritable disorder. Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells. In general, by transfusing healthy stem cells to the recipient's bloodstream to reform a healthy immune system, allogeneic HSCTs appear to improve chances for cure or long-term remission once the immediate transplant-related complications are resolved.[15][16][17]

A compatible donor is found by doing additional HLA-testing from the blood of potential donors. The HLA genes fall in two categories (Type I and Type II). In general, mismatches of the Type-I genes (i.e. HLA-A, HLA-B, or HLA-C) increase the risk of graft rejection. A mismatch of an HLA Type II gene (i.e. HLA-DR, or HLA-DQB1) increases the risk of graft-versus-host disease. In addition a genetic mismatch as small as a single DNA base pair is significant so perfect matches require knowledge of the exact DNA sequence of these genes for both donor and recipient. Leading transplant centers currently perform testing for all five of these HLA genes before declaring that a donor and recipient are HLA-identical.

Race and ethnicity are known to play a major role in donor recruitment drives, as members of the same ethnic group are more likely to have matching genes, including the genes for HLA.[18]

As of 2013[update], there were at least two commercialized allogeneic cell therapies, Prochymal and Cartistem.[19]

To limit the risks of transplanted stem cell rejection or of severe graft-versus-host disease in allogeneic HSCT, the donor should preferably have the same human leukocyte antigens (HLA) as the recipient. About 25 to 30 percent of allogeneic HSCT recipients have an HLA-identical sibling. Even so-called "perfect matches" may have mismatched minor alleles that contribute to graft-versus-host disease.

In the case of a bone marrow transplant, the HSC are removed from a large bone of the donor, typically the pelvis, through a large needle that reaches the center of the bone. The technique is referred to as a bone marrow harvest and is performed under general anesthesia.

Peripheral blood stem cells[20] are now the most common source of stem cells for HSCT. They are collected from the blood through a process known as apheresis. The donor's blood is withdrawn through a sterile needle in one arm and passed through a machine that removes white blood cells. The red blood cells are returned to the donor. The peripheral stem cell yield is boosted with daily subcutaneous injections of Granulocyte-colony stimulating factor, serving to mobilize stem cells from the donor's bone marrow into the peripheral circulation.

It is also possible to extract stem cells from amniotic fluid for both autologous or heterologous use at the time of childbirth.

Umbilical cord blood is obtained when a mother donates her infant's umbilical cord and placenta after birth. Cord blood has a higher concentration of HSC than is normally found in adult blood. However, the small quantity of blood obtained from an Umbilical Cord (typically about 50 mL) makes it more suitable for transplantation into small children than into adults. Newer techniques using ex-vivo expansion of cord blood units or the use of two cord blood units from different donors allow cord blood transplants to be used in adults.

Cord blood can be harvested from the Umbilical Cord of a child being born after preimplantation genetic diagnosis (PGD) for human leucocyte antigen (HLA) matching (see PGD for HLA matching) in order to donate to an ill sibling requiring HSCT.

Unlike other organs, bone marrow cells can be frozen (cryopreserved) for prolonged periods without damaging too many cells. This is a necessity with autologous HSC because the cells must be harvested from the recipient months in advance of the transplant treatment. In the case of allogeneic transplants, fresh HSC are preferred in order to avoid cell loss that might occur during the freezing and thawing process. Allogeneic cord blood is stored frozen at a cord blood bank because it is only obtainable at the time of childbirth. To cryopreserve HSC, a preservative, DMSO, must be added, and the cells must be cooled very slowly in a controlled-rate freezer to prevent osmotic cellular injury during ice crystal formation. HSC may be stored for years in a cryofreezer, which typically uses liquid nitrogen.

The chemotherapy or irradiation given immediately prior to a transplant is called the conditioning regimen, the purpose of which is to help eradicate the patient's disease prior to the infusion of HSC and to suppress immune reactions. The bone marrow can be ablated (destroyed) with dose-levels that cause minimal injury to other tissues. In allogeneic transplants a combination of cyclophosphamide with total body irradiation is conventionally employed. This treatment also has an immunosuppressive effect that prevents rejection of the HSC by the recipient's immune system. The post-transplant prognosis often includes acute and chronic graft-versus-host disease that may be life-threatening. However, in certain leukemias this can coincide with protection against cancer relapse owing to the graft versus tumor effect.[21]Autologous transplants may also use similar conditioning regimens, but many other chemotherapy combinations can be used depending on the type of disease.

A newer treatment approach, non-myeloablative allogeneic transplantation, also termed reduced-intensity conditioning (RIC), uses doses of chemotherapy and radiation too low to eradicate all the bone marrow cells of the recipient.[22]:320321 Instead, non-myeloablative transplants run lower risks of serious infections and transplant-related mortality while relying upon the graft versus tumor effect to resist the inherent increased risk of cancer relapse.[23][24] Also significantly, while requiring high doses of immunosuppressive agents in the early stages of treatment, these doses are less than for conventional transplants.[25] This leads to a state of mixed chimerism early after transplant where both recipient and donor HSC coexist in the bone marrow space.

Decreasing doses of immunosuppressive therapy then allows donor T-cells to eradicate the remaining recipient HSC and to induce the graft versus tumor effect. This effect is often accompanied by mild graft-versus-host disease, the appearance of which is often a surrogate marker for the emergence of the desirable graft versus tumor effect, and also serves as a signal to establish an appropriate dosage level for sustained treatment with low levels of immunosuppressive agents.

Because of their gentler conditioning regimens, these transplants are associated with a lower risk of transplant-related mortality and therefore allow patients who are considered too high-risk for conventional allogeneic HSCT to undergo potentially curative therapy for their disease. The optimal conditioning strategy for each disease and recipient has not been fully established, but RIC can be used in elderly patients unfit for myeloablative regimens, for whom a higher risk of cancer relapse may be acceptable.[22][24]

After several weeks of growth in the bone marrow, expansion of HSC and their progeny is sufficient to normalize the blood cell counts and re-initiate the immune system. The offspring of donor-derived hematopoietic stem cells have been documented to populate many different organs of the recipient, including the heart, liver, and muscle, and these cells had been suggested to have the abilities of regenerating injured tissue in these organs. However, recent research has shown that such lineage infidelity does not occur as a normal phenomenon[citation needed].

HSCT is associated with a high treatment-related mortality in the recipient (1 percent or higher)[citation needed], which limits its use to conditions that are themselves life-threatening. Major complications are veno-occlusive disease, mucositis, infections (sepsis), graft-versus-host disease and the development of new malignancies.

Bone marrow transplantation usually requires that the recipient's own bone marrow be destroyed ("myeloablation"). Prior to "engraftment" patients may go for several weeks without appreciable numbers of white blood cells to help fight infection. This puts a patient at high risk of infections, sepsis and septic shock, despite prophylactic antibiotics. However, antiviral medications, such as acyclovir and valacyclovir, are quite effective in prevention of HSCT-related outbreak of herpetic infection in seropositive patients.[26] The immunosuppressive agents employed in allogeneic transplants for the prevention or treatment of graft-versus-host disease further increase the risk of opportunistic infection. Immunosuppressive drugs are given for a minimum of 6-months after a transplantation, or much longer if required for the treatment of graft-versus-host disease. Transplant patients lose their acquired immunity, for example immunity to childhood diseases such as measles or polio. For this reason transplant patients must be re-vaccinated with childhood vaccines once they are off immunosuppressive medications.

Severe liver injury can result from hepatic veno-occlusive disease (VOD). Elevated levels of bilirubin, hepatomegaly and fluid retention are clinical hallmarks of this condition. There is now a greater appreciation of the generalized cellular injury and obstruction in hepatic vein sinuses, and hepatic VOD has lately been referred to as sinusoidal obstruction syndrome (SOS). Severe cases of SOS are associated with a high mortality rate. Anticoagulants or defibrotide may be effective in reducing the severity of VOD but may also increase bleeding complications. Ursodiol has been shown to help prevent VOD, presumably by facilitating the flow of bile.

The injury of the mucosal lining of the mouth and throat is a common regimen-related toxicity following ablative HSCT regimens. It is usually not life-threatening but is very painful, and prevents eating and drinking. Mucositis is treated with pain medications plus intravenous infusions to prevent dehydration and malnutrition.

Graft-versus-host disease (GVHD) is an inflammatory disease that is unique to allogeneic transplantation. It is an attack of the "new" bone marrow's immune cells against the recipient's tissues. This can occur even if the donor and recipient are HLA-identical because the immune system can still recognize other differences between their tissues. It is aptly named graft-versus-host disease because bone marrow transplantation is the only transplant procedure in which the transplanted cells must accept the body rather than the body accepting the new cells.[27]

Acute graft-versus-host disease typically occurs in the first 3 months after transplantation and may involve the skin, intestine, or the liver. High-dose corticosteroids such as prednisone are a standard treatment; however this immuno-suppressive treatment often leads to deadly infections. Chronic graft-versus-host disease may also develop after allogeneic transplant. It is the major source of late treatment-related complications, although it less often results in death. In addition to inflammation, chronic graft-versus-host disease may lead to the development of fibrosis, or scar tissue, similar to scleroderma; it may cause functional disability and require prolonged immunosuppressive therapy. Graft-versus-host disease is usually mediated by T cells, which react to foreign peptides presented on the MHC of the host.[citation needed]

Graft versus tumor effect (GVT) or "graft versus leukemia" effect is the beneficial aspect of the Graft-versus-Host phenomenon. For example, HSCT patients with either acute, or in particular chronic, graft-versus-host disease after an allogeneic transplant tend to have a lower risk of cancer relapse.[28][29] This is due to a therapeutic immune reaction of the grafted donor T lymphocytes against the diseased bone marrow of the recipient. This lower rate of relapse accounts for the increased success rate of allogeneic transplants, compared to transplants from identical twins, and indicates that allogeneic HSCT is a form of immunotherapy. GVT is the major benefit of transplants that do not employ the highest immuno-suppressive regimens.

Graft versus tumor is mainly beneficial in diseases with slow progress, e.g. chronic leukemia, low-grade lymphoma, and some cases multiple myeloma. However, it is less effective in rapidly growing acute leukemias.[30]

If cancer relapses after HSCT, another transplant can be performed, infusing the patient with a greater quantity of donor white blood cells (Donor lymphocyte infusion).[30]

Patients after HSCT are at a higher risk for oral carcinoma. Post-HSCT oral cancer may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-HSCT patients.[31]

Prognosis in HSCT varies widely dependent upon disease type, stage, stem cell source, HLA-matched status (for allogeneic HSCT) and conditioning regimen. A transplant offers a chance for cure or long-term remission if the inherent complications of graft versus host disease, immuno-suppressive treatments and the spectrum of opportunistic infections can be survived.[15][16] In recent years, survival rates have been gradually improving across almost all populations and sub-populations receiving transplants.[32]

Mortality for allogeneic stem cell transplantation can be estimated using the prediction model created by Sorror et al.,[33] using the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI). The HCT-CI was derived and validated by investigators at the Fred Hutchinson Cancer Research Center (Seattle, WA). The HCT-CI modifies and adds to a well-validated comorbidity index, the Charlson Comorbidity Index (CCI) (Charlson et al.[34]) The CCI was previously applied to patients undergoing allogeneic HCT but appears to provide less survival prediction and discrimination than the HCT-CI scoring system.

The risks of a complication depend on patient characteristics, health care providers and the apheresis procedure, and the colony-stimulating factor used (G-CSF). G-CSF drugs include filgrastim (Neupogen, Neulasta), and lenograstim (Graslopin).

Filgrastim is typically dosed in the 10 microgram/kg level for 45 days during the harvesting of stem cells. The documented adverse effects of filgrastim include splenic rupture (indicated by left upper abdominal or shoulder pain, risk 1 in 40000), Adult respiratory distress syndrome (ARDS), alveolar hemorrage, and allergic reactions (usually expressed in first 30 minutes, risk 1 in 300).[35][36][37] In addition, platelet and hemoglobin levels dip post-procedure, not returning to normal until one month.[37]

The question of whether geriatrics (patients over 65) react the same as patients under 65 has not been sufficiently examined. Coagulation issues and inflammation of atherosclerotic plaques are known to occur as a result of G-CSF injection. G-CSF has also been described to induce genetic changes in mononuclear cells of normal donors.[36] There is evidence that myelodysplasia (MDS) or acute myeloid leukaemia (AML) can be induced by GCSF in susceptible individuals.[38]

Blood was drawn peripherally in a majority of patients, but a central line to jugular/subclavian/femoral veins may be used in 16 percent of women and 4 percent of men. Adverse reactions during apheresis were experienced in 20 percent of women and 8 percent of men, these adverse events primarily consisted of numbness/tingling, multiple line attempts, and nausea.[37]

A study involving 2408 donors (1860 years) indicated that bone pain (primarily back and hips) as a result of filgrastim treatment is observed in 80 percent of donors by day 4 post-injection.[37] This pain responded to acetaminophen or ibuprofen in 65 percent of donors and was characterized as mild to moderate in 80 percent of donors and severe in 10 percent.[37] Bone pain receded post-donation to 26 percent of patients 2 days post-donation, 6 percent of patients one week post-donation, and <2 percent 1 year post-donation. Donation is not recommended for those with a history of back pain.[37] Other symptoms observed in more than 40 percent of donors include myalgia, headache, fatigue, and insomnia.[37] These symptoms all returned to baseline 1 month post-donation, except for some cases of persistent fatigue in 3 percent of donors.[37]

In one metastudy that incorporated data from 377 donors, 44 percent of patients reported having adverse side effects after peripheral blood HSCT.[38] Side effects included pain prior to the collection procedure as a result of GCSF injections, post-procedural generalized skeletal pain, fatigue and reduced energy.[38]

A study that surveyed 2408 donors found that serious adverse events (requiring prolonged hospitalization) occurred in 15 donors (at a rate of 0.6 percent), although none of these events were fatal.[37] Donors were not observed to have higher than normal rates of cancer with up to 48 years of follow up.[37] One study based on a survey of medical teams covered approximately 24,000 peripheral blood HSCT cases between 1993 and 2005, and found a serious cardiovascular adverse reaction rate of about 1 in 1500.[36] This study reported a cardiovascular-related fatality risk within the first 30 days HSCT of about 2 in 10000. For this same group, severe cardiovascular events were observed with a rate of about 1 in 1500. The most common severe adverse reactions were pulmonary edema/deep vein thrombosis, splenic rupture, and myocardial infarction. Haematological malignancy induction was comparable to that observed in the general population, with only 15 reported cases within 4 years.[36]

Georges Math, a French oncologist, performed the first European bone marrow transplant in November 1958 on five Yugoslavian nuclear workers whose own marrow had been damaged by irradiation caused by a criticality accident at the Vina Nuclear Institute, but all of these transplants were rejected.[39][40][41][42][43] Math later pioneered the use of bone marrow transplants in the treatment of leukemia.[43]

Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in Physiology or Medicine. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. His work also reduced the likelihood of developing a life-threatening complication called graft-versus-host disease.[44]

The first physician to perform a successful human bone marrow transplant on a disease other than cancer was Robert A. Good at the University of Minnesota in 1968.[45] In 1975, John Kersey, M.D., also of the University of Minnesota, performed the first successful bone marrow transplant to cure lymphoma. His patient, a 16-year-old-boy, is today the longest-living lymphoma transplant survivor.[46]

At the end of 2012, 20.2 million people had registered their willingness to be a bone marrow donor with one of the 67 registries from 49 countries participating in Bone Marrow Donors Worldwide. 17.9 million of these registered donors had been ABDR typed, allowing easy matching. A further 561,000 cord blood units had been received by one of 46 cord blood banks from 30 countries participating. The highest total number of bone marrow donors registered were those from the USA (8.0 million), and the highest number per capita were those from Cyprus (15.4 percent of the population).[47]

Within the United States, racial minority groups are the least likely to be registered and therefore the least likely to find a potentially life-saving match. In 1990, only six African-Americans were able to find a bone marrow match, and all six had common European genetic signatures.[48]

Africans are more genetically diverse than people of European descent, which means that more registrations are needed to find a match. Bone marrow and cord blood banks exist in South Africa, and a new program is beginning in Nigeria.[48] Many people belonging to different races are requested to donate as there is a shortage of donors in African, Mixed race, Latino, Aboriginal, and many other communities.

In 2007, a team of doctors in Berlin, Germany, including Gero Htter, performed a stem cell transplant for leukemia patient Timothy Ray Brown, who was also HIV-positive.[49] From 60 matching donors, they selected a [CCR5]-32 homozygous individual with two genetic copies of a rare variant of a cell surface receptor. This genetic trait confers resistance to HIV infection by blocking attachment of HIV to the cell. Roughly one in 1000 people of European ancestry have this inherited mutation, but it is rarer in other populations.[50][51] The transplant was repeated a year later after a leukemia relapse. Over three years after the initial transplant, and despite discontinuing antiretroviral therapy, researchers cannot detect HIV in the transplant recipient's blood or in various biopsies of his tissues.[52] Levels of HIV-specific antibodies have also declined, leading to speculation that the patient may have been functionally cured of HIV. However, scientists emphasise that this is an unusual case.[53] Potentially fatal transplant complications (the "Berlin patient" suffered from graft-versus-host disease and leukoencephalopathy) mean that the procedure could not be performed in others with HIV, even if sufficient numbers of suitable donors were found.[54][55]

In 2012, Daniel Kuritzkes reported results of two stem cell transplants in patients with HIV. They did not, however, use donors with the 32 deletion. After their transplant procedures, both were put on antiretroviral therapies, during which neither showed traces of HIV in their blood plasma and purified CD4 T cells using a sensitive culture method (less than 3 copies/mL). However, the virus was once again detected in both patients some time after the discontinuation of therapy.[56]

Since McAllister's 1997 report on a patient with multiple sclerosis (MS) who received a bone marrow transplant for CML,[57] over 600 reports have been published describing HSCTs performed primarily for MS.[58] These have been shown to "reduce or eliminate ongoing clinical relapses, halt further progression, and reduce the burden of disability in some patients" that have aggressive highly active MS, "in the absence of chronic treatment with disease-modifying agents".[58]

Clincs performing HSCT includes Northwestern University and Karolinska University Hospital.

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Hematopoietic stem cell transplantation - Wikipedia

Stem Cell Treatment for Cerebral Palsy

At Beike, our treatment not only focuses on treating the patient current symtoms but also prevents future complications. As cerebral palsy patients mature, the primary symptoms will inevitably lead to futher physical issues that could possibly be avoided.

Possible Improvements after Stem Cell Treatment:

Now lets talk about the stem cells we use in our treatment protocol for Cerebral Palsy.

What are Stem Cells? Stem cells are undifferentiated cells that have the ability to help perform a variety of regenerative functions such as differentiate and replace a wide range of cells in patients body, regulate the immune system and stimulate patients own stem cells. Adult Stem Cells (ACSs) are naturally present in every human being and their task is to regenerate dead and damaged cells during the bodys whole life span. They regenerate cells that are naturally dying (apoptosis) as well as cells injured by other reasons (disease, traumatic injuries etc.). These stem cells have limited differentiation and proliferation potentials, thus they are not likely to create any tumor or cancer. At Beike Biotech, we are only using Umbilical Cord Blood Stem Cells (UCBSC) and Umbilical Cord Mesenchymal Stem Cells (UCMSC) in our treatment protocols, which are 2 types of Adult Stem Cells widely documented and considered as safe by the international scientific community.

How do our Stem Cells help treat Cerebral Palsy? Stem Cells help Cerebral Palsy patients by rebuilding and regenerating the cells that were lost at birth due to a lack of oxygen. These cells will NEVER be naturally regenerated by the body which means the damage that has been done, will NEVER improve.

Is Stem Cell Treatment for Cerebral Palsy Safe? YES Since the companys founding in 2005, more than 20,500 patients (as of January 2016) have been treated with Beikes stem cell technology with no serious adverse outcomes or reactions that have been related to the stem cell transplants. Our medical department doctors review in-depth medical information provided by patients and it is only after this review that patients may be accepted for treatment. All medical procedures present possibility for complications.

As you already know by seeking treatment for Cerebral Palsy, the traditional process of treating Cerebral Palsy is almost as complex as the condition itself. Cerebral Palsy is caused by a lack of oxygen to the brain during birth, being born premature, serious head injuries or infections such as Meningitis. Cerebral Palsy treatment and the everyday life complications are emotionally, physiologically, physically, financially and spiritually draining. The average lifetime cost of treating a child with Cerebral Palsy is $921,000USD, that cost does not include out-of-pocket expenses, visits to the emergency room, lost wages or physosocial effects. Unfortunately, there is no known cure for Cerebral Palsy, conventional treatments options for parents are:

When considering treatment for Cerebral Palsy we focus on all factors that truly determine the level of care the patient needs, also, what a successful outcome would be. It is also important to note that each case of Cerebral Palsy is unique, with unique medical needs for each patient. An example of being able to determine a successful outcome would be as follows; there is no known cure for Cerebral Palsy, so to have the expectation of curing the disease is unrealistic. However, we break down Cerebral Palsy into primary and secondary conditions we are able to identify a realistic treatment outcome, with measurable medical outcomes. An example of a typical primary condition is when a patient has facial muscle control and coordination problems. The facial issues would be considered a primary condition with the secondary conditions being:

Common symptoms caused by Cerebral Palsy

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Stem Cell Treatment for Cerebral Palsy

Induced Pluripotent Stem Cells – cellapplications.com

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Human Induced Pluripotent Stem Cells (HiPSC) Top: HiPSC express pluriotency markers OCT4, Nanog, LIN28 and SSEA-4. Bottom: HiPSC differentiate into cell derivatives from the 3 embryonic layers: Neuronal marker beta III tubulin (TUJ1), Smooth Muscle Actin (SMA) and Hepatocyte Nuclear Factor 3 Beta (HNF3b).

Cell Applications, Inc. has a deep, rich history in HiPSC

Human Dermal Fibroblasts (HDF) from Cell Applications were used by Nobel Laureate S. Yamanaka to establish iPSC in his groundbreaking publications in 2007, unleashing a revolution in stem cell biology. Yamanaka and collaborators demonstrated that expression of four transcription factors widely prevalent in embryonic stem cells is sufficient to trigger the transition of somatic cells towards a pluripotent state that resembles embryonic stem cells in many aspects, such as the expression of classic pluripotency markers and the ability to generate cell derivatives from the three embryonic germ layers.

HiPSC are generated from somatic cells, eliminating ethical considerations associated with scientific work based on embryonic stem cells. Furthermore, being donor/patient-specific, they open possibilities for a wide variety of studies in biomedical research. Donor somatic cells carry the genetic makeup of the diseased patient, hence HiPSC can be used directly to model disease on a dish.

Thus, one of the main uses of HiPSC has been in genetic disease modeling in organs and tissues, such as the brain (Alzheimers, Autism Spectrum Disorders), heart (Familial Hypertrophic, Dilated, and Arrhythmogenic Right Ventricular Cardiomyopathies), and skeletal muscle (Amyotrophic Lateral Sclerosis, Spinal Muscle Atrophy). The combination of HiPSC technology and gene editing strategies such as the CRISPR/Cas9 system creates a powerful platform in which disease-causing mutations can be created on demand and sets of isogenic cell lines (with and without mutations) serve as convenient tools for disease modeling studies.

Other applications of HiPSC and iPSC-differentiated cells include drug screening, development, efficacy and toxicity assessment. As an example, through the FDA-backed CiPA (Comprehensive in vitro Pro-Arrhythmia Assessment) initiative, HiPSC-derived cardiac muscle cells (cardiomyocytes) are poised to constitute a new standard model for the evaluation of cardiotoxicity of new drugs, which is the main reason of drug withdrawal from the market. Finally, HiPSC-differentiated cells are being used in early stage technology development for applications in regenerative medicine. Bio-printing and tissue constructs have also been considered as attractive applications for HiPSC.

StemoniX

Our partner StemoniX is a cutting-edge biotechnology company that is leading the development and manufacturing of HiPSC. They generate biologically accurate miniaturized organ microtissue for academic and industrial pharmaceutical research and discovery. StemoniX, a licensee of Academia Japans iPS patent portfolio, provides high quality HiPSC cells to researchers around the world. StemoniX HiPSC are thoroughly characterized for pluripotency with established pluripotency markers. Proven technology incorporating the latest innovations is able to provide cardiomyocytes with in vitro-like features. Confirmative tests show the HiPSC differentiate into derivatives from the 3 embryonic layers.

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Induced Pluripotent Stem Cells - cellapplications.com

Live Cell Imaging of Induced Pluripotent Stem Cell …

Our live cell image program supports the advancement of iPSC technology in three ways:

1) Identification of process control measurements: A critical component to the translation of iPSCs into therapeutic applications is to design principles for predictably and reproducibly culturing cells and efficiently differentiating them into cell types of interest. Live cell imaging provides high-resolution measurements in the sense that we collect time-dependent data from large numbers of individual cells. We then use this data to discover lower resolution measurements, such as the activity of a biomarker at a single point in time, that can serve as critical process control points during processing of pluripotent stem cells.

2) Interpreting biomarkers: Cells are stochastic and dynamic and may interconvert between states and the expression of biomarkers can change over time. The predictive power of a biomarker or a set of biomarkers the indicate the differentiated state of a cell can be evaluated by examining the history of that cell by tracking forward and backward in time through a time lapse image set.

3) Predictive modeling: We have shown that fluctuations in promoter activity can be used in combination with appropriate models to predict rates of state change in cell populations. Similar mathematical models that can inform bioprocessing decisions during scale-up will be critical to obtaining iPSC populations with a desired set of characteristics.

Over the past several years, we have developed tools for measuring parameters related to size, shape and intensity from single cells over time (Halter Cytometry 2011). We have also developed modeling tools for using the temporal information to model the stochastic and deterministic components of gene expression (Sisan PNAS 2012; Lund Phys Chem B 2014).

We are now applying these live cell imaging tools to the study of stem cell pluripotency and differentiation (Bhadriraju Stem Cell Research 2016). Induced pluripotent stem cell technologies are a powerful new tool for biomedical research and have the potential to revolutionize medicine.

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Live Cell Imaging of Induced Pluripotent Stem Cell ...

Induced pluripotent stem cell models from X-linked …

Objective:

Because of a lack of an appropriate animal model system and the inaccessibility of human oligodendrocytes in vivo, X-linked adrenoleukodystrophy (X-ALD)-induced pluripotent stem cells (iPSCs) would provide a unique cellular model for studying etiopathophysiology and development of therapeutics for X-ALD.

We generated and characterized iPSCs of the 2 major types of X-ALD, childhood cerebral ALD (CCALD) and adrenomyeloneuropathy (AMN), and differentiated them into oligodendrocytes and neurons. We evaluated disease-relevant phenotypes by pharmacological and genetic approaches.

We established iPSCs from the patients with CCALD and AMN. Both CCALD and AMN iPSCs normally differentiated into oligodendrocytes, the cell type primarily affected in the X-ALD brain, indicating no developmental defect due to the ABCD1 mutations. Although low in X-ALD iPSCs, very long chain fatty acid (VLCFA) level was significantly increased after oligodendrocyte differentiation. VLCFA accumulation was much higher in CCALD oligodendrocytes than AMN oligodendrocytes but was not significantly different between CCALD and AMN neurons, indicating that the severe clinical manifestations in CCALD might be associated with abnormal VLCFA accumulation in oligodendrocytes. Furthermore, the abnormal accumulation of VLCFA in the X-ALD oligodendrocytes can be reduced by the upregulated ABCD2 gene expression after treatment with lovastatin or 4-phenylbutyrate.

X-ALD iPSC model recapitulates the key events of disease development (ie, VLCFA accumulation in oligodendrocytes), provides new clues for better understanding of the disease, and allows for early and accurate diagnosis of the disease subtypes. X-ALD oligodendrocytes can be a useful cell model system to develop new therapeutics for treating X-ALD. ANN NEUROL 2011;

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Induced pluripotent stem cell models from X-linked ...

Medi-Cal: Medi-Cal Update – Clinics and Hospitals | May …

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Effective retroactively for dates of service on or after November 1, 2015, reimbursement for factor X preparations requires a separate Service Authorization Request (SAR) for the California Children's Services (CCS)/Genetically Handicapped Persons Program (GHPP).

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, the current HCPCS Local Level III codes for Home Health Agencies (HHA) will be discontinued. The codes will be replaced by 11 new Health Insurance Portability and Accountability Act (HIPAA) compliant national and revenue codes. The HCPCS national code and revenue code will be required on all home health claims.

Every new Treatment Authorization Request (TAR) and electronic TAR (eTAR) submitted with dates of service on or after June 1, 2016, must include the HCPCS codes described below; the revenue code is not required. The Department of Health Care Services (DHCS) will provide directions at regular intervals, reminding providers to exhaust existing TARs and Service Authorization Requests (SARs).

Providers should review their inventory for previously approved TARs with HHA services that have dates of service on or after June 1, 2016. For those TARs, providers must submit a new TAR or eTAR with the appropriate HCPCS code to cover any remaining service period on or after June 1, 2016.

If the submitted TAR is for the purpose of updating the codes for the same authorization period, it will not be reviewed for medical necessity.

The conversion is as follows:

Includes supplies that are used as part of the treatment visit.

No limit on the number of daily visits.

Limited to 40 15-minute increments per day

Limited to one visit per day or four 15-minute increments.

Limited to one visit per day or four 15-minute increments.

Limited to one visit per day or four 15-minute increments.

Limited to one visit per day or four 15-minute increments.

Respiratory therapist services can be authorized and billed under 99600.

CPT-4 code 99502 Home visit for newborn care and assessment

Does not require a TAR.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after April 1, 2016, the following diabetes self-management training (DSMT) HCPCS codes are Medi-Cal benefits:

The frequency restrictions for claims paid in the first continuous 12 months (one year) and subsequent years have been updated in the provider manual.

Claims with additional number of hours are to be billed with a Treatment Authorization Request (TAR), California Children's Services (CCS)/Genetically Handicapped Persons Program (GHPP) stamp or CCS Service Authorization Request (SAR).

HCPCS codes G0108 and G0109 may not be billed on the same date of service as CPT-4 codes 97802 97804.

Effective for dates of service on or after April 1, 2016, the following medical nutrition therapy (MNT) CPT-4 codes are Medi-Cal benefits:

Claims with additional number of hours are to be billed with a TAR, CSS/GHPP stamp, or CCS SAR.

CPT-4 codes 97802 97804 may not be billed on the same date of service as HCPCS codes G0108 and G0109.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, genetic testing for maturity onset diabetes of the young (MODY) is reimbursable under the following CPT-4 codes as a new Medi-Cal benefit:

Reimbursement for MODY requires an approved Treatment Authorization Request (TAR) and requires providers to document the following on the TAR:

This information is reflected in the following provider manual(s):

Effective retroactively for dates of service on or after October 1, 2015, select HCPCS and CPT-4 codes are no longer split billable. Claim lines with the following codes must not be billed with modifiers 26, TC or 99, and do not require a modifier:

This information is reflected in the following provider manual(s):

Effective retroactively for dates of service on or after September 1, 2012, policy language and billing instructions are updated in the provider manual for Healthcare Common Procedure System (HCPCS) codes J1950 (injection, leuprolide acetate [for depot suspension], per 3.75 mg) and J9217 (leuprolide acetate [for depot suspension], 7.5 mg).

For claims denied with dates of service on or after September 1, 2012, providers may submit new claims for denials due to incorrect coding of HCPCS codes J1950 or J9217. Providers may also submit new claims for denials due to incorrect billing with J9217 in place of J1950 or vice versa. To initiate a new claim, providers must submit a Claims Inquiry Form (CIF) to void the previously denied claim. Both the CIF and new claim must be submitted together.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after January 1, 2016, HCPCS code J9299 (injection, nivolumab, 1 mg) replaces terminated HCPCS code C9453 (injection, nivolumab, 1 mg). The following are indications for the treatment of patients 18 years of age and older:

Recommended dosage instructions vary dependent upon the administration combination with ipilimumab.

The code requires an approved Treatment Authorization Request (TAR). Affected claims will be reprocessed.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, policy for HCPCS code J9047 (injection, carfilzomib, 1 mg) has been updated.

Carfilzomib is indicated for the treatment of multiple myeloma and is limited to patients 18 years of age and older.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after July 1, 2016, HCPCS codes C9137 (injection, factor VIII [antihemophilic factor, recombinant] PEGylated, 1 I.U.) and C9138 (injection, factor VIII [antihemophilic factor, recombinant] [Nuwiq], 1 I.U.) are Medi-Cal benefits. To bill for injection, factor VIII or injection, factor VIII (Nuqwiq), providers should now use codes C9137 and C9138, respectively, instead of HCPCS code J7199 (hemophilia clotting factor, not otherwise classified).

This information is reflected in the following provider manual(s):

Effective January 1, 2016, through December 31, 2016, Presumptive Eligibility (PE) for Pregnant Women providers must use the following income eligibility guidelines to make PE for Pregnant Women determinations.

This information is reflected in the following provider manual(s):

The Department of Health Care Services (DHCS) identified a claims processing issue causing claims billed with the following CPT-4 codes to deny when billed in conjunction with ICD-10-CM diagnosis codes O09.521 O09.523 (supervision of elderly multigravida):

This issue affects claims with dates of service on or after October 1, 2015.

DHCS will notify providers when the issue is resolved. Providers should continue to submit claims timely. Affected claims will be reprocessed via an Erroneous Payment Correction (EPC). Providers are encouraged to check the Medi-Cal website regularly for updates regarding this issue.

An article in the February 2016 Medi-Cal Update announced that, effective for dates of service on or after March 1, 2016, reimbursement for screening mammograms is restricted to females 50 to 74 years of age. This announcement was not compliant with the Consolidated Appropriations Act of 2016 (House Resolution 2029).

Providers should continue to supply mammography services. Breast cancer screening mammography for females 40 years of age and older, by any provider, once a year is reimbursable.

Retroactive to September 1, 2013, Medi-Cal's policy on reimbursement for screening mammograms is consistent with the U.S. Preventive Services Task Force's 2002 recommendation of breast cancer screening mammography every year for women 40 years of age and older. The revised policy applies to the following codes:

There are no diagnostic restrictions for screening mammograms. An approved Treatment Authorization Request (TAR) may override gender restrictions. Providers should continue to submit claims timely.

Denied claims for males for codes 77052, 77057 and G0202 will be reviewed retroactive to September 1, 2013. If authorization was documented, these claims will be reprocessed through the Erroneous Payment Correction (EPC) process.

Providers should continue to check the Medi-Cal website regularly for updates.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, CPT-4 codes 81519 (oncology [breast], mRNA, gene expression profiling by real-time RT-PCR of 21 genes, utilizing formalin-fixed paraffin embedded tissue, algorithm reported as recurrence score) and 81599 (unlisted multinalyte assay with algorithmic analysis) are Medi-Cal benefits.

Codes 81519 and 81599 have a frequency limit of once in a lifetime and require a Treatment Authorization Request (TAR) with documentation of the following:

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, a sterilization Consent Form (PM 330) and an approved Treatment Authorization Request (TAR) are required for the following CPT-4 codes, when the procedure will result in sterilization:

For all procedures that ensure sterilization, including unilateral procedures for patients who only have one ovary, testicle or vas, a PM 330 is required. Additional information about requirements for these procedures is located in the Sterilization section of the Part 2 provider manual.

This information is reflected in the following provider manual(s):

Bayer Corporation acquired Conceptus in 2013. Bayer provides the Essure System ESS305, a micro-insert procedure billed under CPT-4 code 58565 (hysteroscopy, surgical; with bilateral fallopian tube cannulation to induce occlusion by placement of permanent implants).

This information is reflected in the following provider manual(s):

Effective for dates of service on or after April 1, 2016, HCPCS code C9461 (choline C 11, diagnostic, per study dose) is a new Medi-Cal benefit. Allowable modifiers are 99 and U7. An invoice is required for reimbursement.

This information is reflected in the following provider manual(s):

Providers are encouraged to access the California Department of Public Healths (CDPH) Zika Web page, which continues to publish updates about Zika virus. Some of the available resources include Zika Virus FAQs for Health Care Providers, a Zika Questions and Answers fact sheet for the general public and a colorful, ready-to-print Zika and Pregnancy poster. Some resources are also available in Spanish.

CDPH asks that providers and their staff #TalkZIKA by sharing and retweeting social media messages. Providers can follow CDPH on Facebook (English and Spanish pages) and Twitter. In addition, providers can promote and provide Zika facts by adding the following clickable graphic to their email signatures, by simply copying the graphic and pasting using the Keep Source Formatting option. Clicking the image opens the CDPH Zika Web page.

Effective for dates of service on or after June 1, 2016, reimbursement for hormone injections used in the treatment of malignant neoplasms does not require an ICD-10-CM diagnosis code.

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, the Department of Health Care Services (DHCS) has updated the Treatment Authorization Request (TAR) requirement for bariatric surgery. This procedure is no longer required to be performed in a Centers for Medicare and Medicaid Services (CMS) certified Center of Excellence (COE).

This information is reflected in the following provider manual(s):

Effective for dates of service on or after June 1, 2016, liver-lung and liver-heart transplants are Medi-Cal benefits. In order to be reimbursable for liver-lung and liver-heart transplantation, the institution must be a Medi-Cal approved Center of Excellence for liver-lung and liver-heart transplants.

Policy Updates for Liver Transplantations

Indications for Liver-Heart and Liver-Lung Transplants

This information is reflected in the following provider manual(s):

Effective retroactively for dates of service on or after November 1, 2014, rates for the following codes have changed:

An Erroneous Payment Correction (EPC) will be implemented to reprocess affected claims.

Effective retroactively for dates of service on or after September 1, 2014, providers billing for CPT-4 code 29125 (application of short arm splint; static) are no longer required to submit an attachment for reimbursement. Providers should bill CPT-4 code 29125 with modifier AG (primary surgeon), SA (nurse practitioner rendering service in collaboration with a physician) or U7 (services rendered by physician assistant) to indicate their provider type.

An Erroneous Payment Correction will be implemented to reprocess affected claims.

A new DUR Educational Article titled Drug Safety Communication: Saxagliptin, Alogliptin and Risk of Heart Failure (PDF format) is available on the DUR: Educational Articles page of the Medi-Cal website.

A new DUR Educational Article titled Clinical Review: Atypical Antipsychotics and Adverse Metabolic Effects (PDF format) is available on the DUR: Educational Articles page of the Medi-Cal website.

A new DUR Educational Article titled Drug Safety Communication: New Safety Warnings Added to Prescription Opioids (PDF format) is available on the DUR: Educational Articles page of the Medi-Cal website.

Effective immediately, unless otherwise directed by Medi-Cal, all paper Treatment Authorization Requests (TARs) should be sent to the following location:

TAR Processing Center 820 Stillwater Road West Sacramento, CA 95605-1630

If a provider submits a TAR to a field office, the TAR will be returned to the provider with instructions to send the TAR to the TAR Processing Center.

For TAR status or issues, providers may call the Telephone Service Center (TSC) at 1-800-541-5555. Providers outside of California may call (916) 636-1980.

Department of Health Care Services (DHCS) offers the Provider Manual on the Medi-Cal website in Microsoft Word format and as a ZIP (compressed file). The website also contains links to free software to view these file formats.

DHCS is exploring modernizing the Medi-Cal, Child Health and Disability Prevention (CHDP) and Family Planning, Access, Care and Treatment (Family PACT) provider manuals to reflect the shift to mobile computing.

This Provider Manual Survey will collect provider feedback on this modernization effort. Responses will help DHCS assess provider concerns about moving toward a more mobile-friendly platform. While participation is not required, DHCS encourages all providers to take the survey. All answered surveys will be kept confidential and anonymous.

The Medi-Cal and specialty program provider manuals include online indexes that assist providers in finding information in the provider manuals. The Medi-Cal website also includes an online search tool that allows providers to quickly search key words and locate appropriate policy information in the provider manuals.

The Department of Health Care Services (DHCS) is exploring an idea to retire the index sections from the Medi-Cal, Child Health and Disability Prevention (CHDP) and Family Planning, Access, Care and Treatment (Family PACT) provider manuals.

DHCS developed the Manual Indexes Survey to collect provider feedback. Responses will help DHCS assess any provider issues or concerns about retiring the indexes. While participation is not required, DHCS encourages all providers to take the survey. All answered surveys will be kept confidential and anonymous.

Providers should note an Acronyms and Abbreviations Glossary section will remain in the provider manuals to assist providers with acronyms, and the Medi-Cal website's search function will still be available for provider use.

Effective for dates of service on or after January 1, 2016, the Medi-Cal claims processing system has been updated to align medical transportation and physician administered drug codes to the National Correct Coding Initiative (NCCI) edits regarding Medically Unlikely Edits (MUEs).

For additional information on NCCI MUEs, providers may refer to the Medically Unlikely Edits page of the Centers for Medicare & Medicaid Services (CMS) website.

The Centers for Medicare & Medicaid Services (CMS) has released the quarterly National Correct Coding Initiative (NCCI) payment policy updates. These mandatory national edits have been incorporated into the Medi-Cal claims processing system and are valid for dates of service on or after April 1, 2016.

For additional information, refer to The National Correct Coding Initiative in Medicaid page of the Medicaid website.

Beginning June 7, 2016, and continuing throughout the month of June, the Department of Health Care Services (DHCS) Fiscal Intermediary, Xerox State Healthcare, LLC (Xerox) invites providers to participate in Medi-Cal provider training webinars. The webinars will be:

Providers will also have the ability to print class materials and ask questions during the training sessions. For those who are unable to attend, all recorded webinars will be archived and made available for viewing on the MLP.

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Medi-Cal: Medi-Cal Update - Clinics and Hospitals | May ...

Generation of germline-competent induced pluripotent stem …

We have previously shown that pluripotent stem cells can be induced from mouse fibroblasts by retroviral introduction of Oct3/4 (also called Pou5f1), Sox2, c-Myc and Klf4, and subsequent selection for Fbx15 (also called Fbxo15) expression. These induced pluripotent stem (iPS) cells (hereafter called Fbx15 iPS cells) are similar to embryonic stem (ES) cells in morphology, proliferation and teratoma formation; however, they are different with regards to gene expression and DNA methylation patterns, and fail to produce adult chimaeras. Here we show that selection for Nanog expression results in germline-competent iPS cells with increased ES-cell-like gene expression and DNA methylation patterns compared with Fbx15 iPS cells. The four transgenes (Oct3/4, Sox2, c-myc and Klf4) were strongly silenced in Nanog iPS cells. We obtained adult chimaeras from seven Nanog iPS cell clones, with one clone being transmitted through the germ line to the next generation. Approximately 20% of the offspring developed tumours attributable to reactivation of the c-myc transgene. Thus, iPS cells competent for germline chimaeras can be obtained from fibroblasts, but retroviral introduction of c-Myc should be avoided for clinical application.

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Generation of germline-competent induced pluripotent stem ...

Platelet Rich Plasma Therapy and Osteoarthritis – PRP …

Recently, emerging evidence has suggested that Platelet Rich Plasma (PRP) may also be of assistance in the treatment of osteoarthritis and other degenerative conditions of joints. It is felt that the growth factors may assist in cartilage regeneration and also mediate benefit by providing an immune modulating effect, whereby the inflammatory cascade is dampened. Thus, PRP may act as a natural anti-inflammatory substance to result in symptomatic pain relief of sore arthritic joints.

The process of obtaining PRP for use in treatment of osteoarthritis of joints is identical to that outlined for PRP injections of tendons.

Patients and referring clinicians may have recently become aware of this procedure in the media: (ACA "New Knees", Friday, August 30, 2013 - http://aca.ninemsn.com.au/article.aspx?id=8715252) and may therefore find our fact sheet on PRP injections of further assistance.

An ultrasound machine is used to guide the safe and accurate delivery of PRP into a patients arthritic knee.

For more information read: Melbourne Radiology Clinic - Patient Fact Sheet: Autologous Blood Injection & Platelet Rich Plasma Injections

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Platelet Rich Plasma Therapy and Osteoarthritis - PRP ...

Induced pluripotent stem-cell therapy – Wikipedia

In 2006, Shinya Yamanaka of Kyoto University in Japan was the first to disprove the previous notion that reversible cell differentiation of mammals was impossible. He reprogrammed a fully differentiated mouse cell into a pluripotent stem cell by introducing four genes, Oct-4, SOX2, KLF4, and Myc, into the mouse fibroblast through gene-carrying viruses. With this method, he and his coworkers created induced pluripotent stem cells (iPS cells), the key component in this experiment.[1] Scientists have been able to conduct experiments that show the ability of iPS cells to treat and even cure diseases. In this experiment, tests were run on mice with inherited sickle-cell anemia. Skin cells were turned into cells containing genes that transformed the cells into iPS cells. These replaced the diseased sickled cells, curing the test mice. The reprogramming of the pluripotent stem cells in mice was successfully duplicated with human pluripotent stem cells within about a year of the experiment on the mice.[citation needed]

Sickle-cell anemia is a disease in which the body produces abnormally shaped red blood cells. Red blood cells are flexible and round, moving easily through the blood vessels. Infected cells are shaped like a crescent or sickle (the namesake of the disease). As a result of this disorder the hemoglobin protein in red blood cells is faulty. Normal hemoglobin bonds to oxygen, then releases it into cells that need it. The blood cell retains its original form and is cycled back to the lungs and re-oxygenated.

Sickle cell hemoglobin, however, after giving up oxygen, cling together and make the red blood cell stiff. The sickle shape also makes it difficult for the red blood cell to navigate arteries and causes blockages.[2] This can cause intense pain and organ damage. The sickled red blood cells are fragile and prone to rupture. When the number of red blood cells decreases from rupture (hemolysis), anemia is the result. Sickle cells die in 1020 days as opposed to the traditional 120-day lifespan of a normal red blood cell.

Sickle cell anemia is inherited as an autosomal (meaning that the gene is not linked to a sex chromosome) recessive condition.[2] This means that the gene can be passed on from a carrier to his or her children. In order for sickle cell anemia to affect a person, the gene must be inherited from both the mother and the father, so that the child has two recessive sickle cell genes (a homozygous inheritance). People who inherit one sickle cell gene from one parent and one normal gene from the other parent, i.e. heterozygous patients, have a condition called sickle cell trait. Their bodies make both sickle hemoglobin and normal hemoglobin. They may pass the trait on to their children.

The effects of sickle-cell anemia vary from person to person. People who have the disease suffer from varying degrees of chronic pain and fatigue. With proper care and treatment, the quality of health of most patients will improve. Doctors have learned a great deal about sickle cell anemia since its discovery in 1979. They know its causes, its effects on the body, and possible treatments for complications. Sickle cell anemia has no widely available cure. A bone marrow transplant is the only treatment method currently recognized to be able to cure the disease, though it does not work for every patient. Finding a donor is difficult and the procedure could potentially do more harm than good. Treatments for sickle cell anemia are generally aimed at avoiding crises, relieving symptoms, and preventing complications. Such treatments may include medications, blood transfusions, and supplemental oxygen.

During the first step of the experiment, skin cells (also known as fibroblasts) were collected from infected test mice and put in a culture. The fibroblasts were reprogrammed by infecting them with retroviruses that contained genes common to embryonic stem cells. These genes were the same four used by Yamanaka (Oct-4, SOX2, KLF4, and Myc) in his earlier study. The investigators were trying to produce cells with the potential to differentiate into any type of cell needed (i.e. pluripotent stem cells). As the experiment continued, the fibroblasts multiplied into identical copies of iPS cells. The cells were then treated to form the mutation needed to reverse the anemia in the mice. This was accomplished by restructuring the DNA containing the defective globin gene into DNA with the normal gene through the process of homologous recombination. The iPS cells then differentiated into blood stem cells, or hematopoietic stem cells. The hematopoietic cells were injected back into the infected mice, where they proliferate and differentiate into normal blood cells, curing the mice of the disease.[3][4][verification needed]

To determine whether the mice were cured from the disease, the scientists checked for the usual symptoms of sickle cell disease. They examined the blood for mean corpuscular volume (MCV) and red cell distribution width (RDW) and urine concentration defects. They also checked for sickled red blood cells. They examined the DNA through gel electrophoresis, checking for bands that display an allele that causes sickling. Compared to the untreated mice with the disease, which they used as a control, "the treated animals had marked increases in RBC counts, healthy hemoglobin, and packed cell volume levels".[5]

Researchers examined "the urine concentration defect, which results from RBC sickling in renal tubules and consequent reduction in renal medullary blood flow, and the general deteriorated systemic condition reflected by lower body weight and increased breathing."[5] They were able to see that these parts of the body of the mice had healed or improved. This indicated that "all hematological and systemic parameters of sickle cell anemia improved substantially and were comparable to those in control mice."[5] They cannot say if this will work in humans because a safe way to inject the genes for the induced pluripotent cells is still needed.[citation needed]

The reprogramming of the induced pluripotent stem cells in mice was successfully duplicated in humans within a year of the successful experiment on the mice. This reprogramming was done in several labs and it was shown that the iPS cells in humans were almost identical to original embryonic stem cells (ES cells) that are responsible for the creation of all structures in a fetus.[1] An important feature of iPS cells is that they can be generated with cells taken from an adult, which would circumvent many of the ethical problems associated with working with ES cells. These iPS cells also have potential in creating and examining new disease models and developing more efficient drug treatments.[6] Another feature of these cells is that they provide researchers with a human cell sample, as opposed to simply using an animal with similar DNA, for drug testing.

One major problem with iPS cells is the way in which the cells are reprogrammed. Using gene-carrying viruses has the potential to cause iPS cells to develop into cancerous cells.[1] Also, an implant made using undifferentiated iPS cells, could cause a teratoma to form. Any implant that is generated from using these iPS cells would only be viable for transplant into the original subject that the cells were taken from. In order for these iPS cells to become viable in therapeutic use, there are still many steps that must be taken.[5][7]

In the future, researchers hope that induced pluripotent cells may be used to treat other diseases. Pluripotency is a crucial part of disease treatment because iPS cells are capable of differentiation in a way that is very similar to embryonic stem cells which can grow into fully differentiated tissues. iPS cells also demonstrate high telomerase activity and express human telomerase reverse transcriptase, a necessary component in the telomerase protein complex. Also, iPS cells expressed cell surface antigenic markers expressed on ES cells. Also, doubling time and mitotic activity are cornerstones of ES cells, as stem cells must self-renew as part of their definition. As said, iPS cells are morphologically similar to embryonic stem cells. Each cell has a round shape, a large nucleolus and a small amount of cytoplasm. One day, the process may be used in practical settings to provide a fundamental way of regeneration.

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Induced pluripotent stem-cell therapy - Wikipedia

Platelet Rich Plasma – L.A. Beauty Skin Center

Is your skin tone simply not as healthy and smooth as on previous occasions? Have you noted fine lines and sagging skin around your eyes, cheeks and mouth? Are you conscious of the puffiness and dark circles below your eyes? The best recommended solution to these types of skin issues is Platelet Rich Plasma therapy. PRP is an advanced treatment technology that utilizes ingredients present in an individuals blood in order to regenerate their skin and revitalize collagen, leading to healthy, young looking skin.

Platelet Rich Plasma has a protracted history of being applied in dentistry, reconstructive surgery and orthopedic medicine. Today, it is also being used in other branches of medicine including dermatology, cosmetic facial rejuvenation and skin wound healing. Scientific studies ever since have proven that PRP generates new collagen when infused into the skin and recent studies reveal that PRP can ease sun damage as well as aging skin problems.

PRP is basically a natural product produced from your own body. Through a simple blood draw, a little amount of blood is drawn from an individual into a sterile tube. Using a unique centrifuge machine, the blood is spun down in order to take out and concentrate the stem cells, growth factors and platelets that are very important for tissue healing. This little amount of blood with a high concentration of platelets and growth factors is referred to as Platelet Rich Plasma (PRP).

PRP is best known for its wonderful act of skin rejuvenation. When PRP is injected into particular parts of the skin, its high platelet concentration functions as a matrix that stimulates the growth of new collagen, revitalizes skin tissue and hence leads to a naturally smooth and firm skin. As a result, PRP treatment gets rid of wrinkles and creates a smoother skin feel and tone.

There is a huge difference between PRP therapy and other skin injections of fillers. Most fillers including Juvederm and Restylane are composed of solid material which fills skin lines and folds. They often last for short period of time and require repeated treatments to seal the area yet again. On the other hand, PRP fuels collagen growth for absolute facial rejuvenation instead of individual wrinkle enhancement. Platelet Rich Plasma therapy is recommended for faces that appear drawn, to soften below eye puffiness, enhance the overall skin tone, texture and tightness and seal skin areas where fillers are not able to reach. Fillers such as Juvederm and Restylane can be applied together with PRP given that the two forms of skin treatment actually serve different purposes. The fillers will fill particular wrinkles while PRP will enhance overall wrinkle improvement.

There is enough evidence to show that Platelet Rich Plasma can be used to treat several skin issues such as Diabetic foot ulcers, bedsores, thermal burns, hair loss, superficial and surgical injuries and skin graft donor sites. Others include facial rejuvenation and post-traumatic scars.

For optimal results, LA Beauty Skin Center is the best place to have your PRP cosmetic treatment. Improvement of the skin tone and elasticity will be visible immediately after treatment. To maintain your skin and face looking young, make follow-up PRP treatments at LA Beauty Skin Center.

Current Price

Full Face + micro needling $950

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Platelet Rich Plasma - L.A. Beauty Skin Center