Category Archives: California Stem Cells

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

BioTime company Asterias Biotherapeutics (NYSE MKT: AST) was granted a $14.3 million Strategic Partnership Award by the California Institute for Regenerative Medicine (CIRM) to re-initiate the worlds first embryonic stem cell-based human clinical trial, for spinal cord injury. Supported by California public funds, CIRM is the largest funder of stem cell-related research and development in the world.[43]

The award provides funding for Asterias to reinitiate clinical development of AST-OPC1 in subjects with spinal cord injury and to expand clinical testing of escalating doses in the target population intended for future pivotal trials.[44]

AST-OPC1 is a population of cells derived from human embryonic stem cells (hESCs) that contains oligodendrocyte progenitor cells (OPCs). OPCs and their mature derivatives called oligodendrocytes provide critical functional support for nerve cells in the spinal cord and brain. Asterias recently presented the results from phase 1 clinical trial testing of a low dose of AST-OPC1 in patients with neurologically-complete thoracic spinal cord injury. The results showed that AST-OPC1 was successfully delivered to the injured spinal cord site. Patients followed 2-3 years after AST-OPC1 administration showed no evidence of serious adverse events associated with the cells in detailed follow-up assessments including frequent neurological exams and MRIs. Immune monitoring of subjects through one year post-transplantation showed no evidence of antibody-based or cellular immune responses to AST-OPC1. In four of the five subjects, serial MRI scans performed throughout the 2-3 year follow-up period indicate that reduced spinal cord cavitation may have occurred and that AST-OPC1 may have had some positive effects in reducing spinal cord tissue deterioration. There was no unexpected neurological degeneration or improvement in the five subjects in the trial as evaluated by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam.[45]

The Strategic Partnership III grant from CIRM will provide funding to Asterias to support the next clinical trial of AST-OPC1 in subjects with spinal cord injury, and for Asterias product development efforts to refine and scale manufacturing methods to support later-stage trials and eventually commercialization. CIRM funding will be conditional on FDA approval for the trial, completion of a definitive agreement between Asterias and CIRM, and Asterias continued progress toward the achievement of certain pre-defined project milestones.[46]

In vitro fertilization generates multiple embryos. The surplus of embryos is not clinically used or is unsuitable for implantation into the patient, and therefore may be donated by the donor with consent. Human embryonic stem cells can be derived from these donated embryos or additionally they can also be extracted from cloned embryos using a cell from a patient and a donated egg.[47] The inner cell mass (cells of interest), from the blastocyst stage of the embryo, is separated from the trophectoderm, the cells that would differentiate into extra-embryonic tissue. Immunosurgery, the process in which antibodies are bound to the trophectoderm and removed by another solution, and mechanical dissection are performed to achieve separation. The resulting inner cell mass cells are plated onto cells that will supply support. The inner cell mass cells attach and expand further to form a human embryonic cell line, which are undifferentiated. These cells are fed daily and are enzymatically or mechanically separated every four to seven days. For differentiation to occur, the human embryonic stem cell line is removed from the supporting cells to form embryoid bodies, is co-cultured with a serum containing necessary signals, or is grafted in a three-dimensional scaffold to result.[48]

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

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

It is now known that the feeder cells provide leukemia inhibitory factor (LIF) and serum provides bone morphogenetic proteins (BMPs) that are necessary to prevent ES cells from differentiating.[49][50] These factors are extremely important for the efficiency of deriving ES cells. Furthermore, it has been demonstrated that different mouse strains have different efficiencies for isolating ES cells.[51] Current uses for mouse ES cells include the generation of transgenic mice, including knockout mice. For human treatment, there is a need for patient specific pluripotent cells. Generation of human ES cells is more difficult and faces ethical issues. So, in addition to human ES cell research, many groups are focused on the generation of induced pluripotent stem cells (iPS cells).[52]

On August 23, 2006, the online edition of Nature scientific journal published a letter by Dr. Robert Lanza (medical director of Advanced Cell Technology in Worcester, MA) stating that his team had found a way to extract embryonic stem cells without destroying the actual embryo.[53] This technical achievement would potentially enable scientists to work with new lines of embryonic stem cells derived using public funding in the USA, where federal funding was at the time limited to research using embryonic stem cell lines derived prior to August 2001. In March, 2009, the limitation was lifted.[54]

In 2007 it was shown that pluripotent stem cells highly similar to embryonic stem cells can be generated by the delivery of three genes (Oct4, Sox2, and Klf4) to differentiated cells.[55] The delivery of these genes "reprograms" differentiated cells into pluripotent stem cells, allowing for the generation of pluripotent stem cells without the embryo. Because ethical concerns regarding embryonic stem cells typically are about their derivation from terminated embryos, it is believed that reprogramming to these "induced pluripotent stem cells" (iPS cells) may be less controversial. Both human and mouse cells can be reprogrammed by this methodology, generating both human pluripotent stem cells and mouse pluripotent stem cells without an embryo.[56]

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

However, as a first indication that the induced pluripotent stem cell (iPS) cell technology can in rapid succession lead to new cures, it was used by a research team headed by Rudolf Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, to cure mice of sickle cell anemia, as reported by Science journal's online edition on December 6, 2007.[57][58]

On January 16, 2008, a California-based company, Stemagen, announced that they had created the first mature cloned human embryos from single skin cells taken from adults. These embryos can be harvested for patient matching embryonic stem cells.[59]

The online edition of Nature Medicine published a study on January 24, 2005, which stated that the human embryonic stem cells available for federally funded research are contaminated with non-human molecules from the culture medium used to grow the cells.[60] It is a common technique to use mouse cells and other animal cells to maintain the pluripotency of actively dividing stem cells. The problem was discovered when non-human sialic acid in the growth medium was found to compromise the potential uses of the embryonic stem cells in humans, according to scientists at the University of California, San Diego.[61]

However, a study published in the online edition of Lancet Medical Journal on March 8, 2005 detailed information about a new stem cell line that was derived from human embryos under completely cell- and serum-free conditions. After more than 6 months of undifferentiated proliferation, these cells demonstrated the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. These properties were also successfully maintained (for more than 30 passages) with the established stem cell lines.[62]

Excerpt from:
Embryonic stem cell - Wikipedia

JaCeon Golden has only ever known the inside of hospitals. But the treatment hes receiving may have implications far beyond his as-yet isolated life.

Round-faced and big-eyed, with a perpetual pout that belies his sunny nature, he looks as healthy as any other 5-month-old. But JaCeon was born without a functioning immune system. Even the most banal of infections a cold, a diaper rash could be deadly.

Earlier this year, JaCeon became the first baby at UCSF Benioff Childrens Hospital at Mission Bay to undergo an experimental gene therapy treatment that, doctors hope, will nudge his body to build a new, robust immune system.

From right: Dannie Hawkins checks on her nephew Ja'Ceon Golden, who is being held by patient care assistant Grace Deng at UCSF Benioff Children's Hospital on Wednesday, March 8, 2017, in San Francisco, Calif. Golden, who is five months old, is diagnosed with severe combined immunodeficiency disease (SCID). He is a patient at UCSF, where he stays in a sterile room. The hospital is working on a new gene therapy treatment for SCID. Hawkins brought her nephew Golden from New Mexico for the experimental treatment.

From right: Dannie Hawkins checks on her nephew Ja'Ceon Golden, who...

So far, his results are promising. In a few weeks, JaCeons great aunt, whos also his guardian, hopes to introduce him to the world outside.

Am I going to see him smile when we walk out of here? Dannie Hawkins, 52, said with a glance at the baby, being fed from a bottle by a nurse wearing a gown and gloves. Hows he going to do in the free world?

It will be a while months, probably years before JaCeon is able to fully integrate with that wide world: go to school and birthday parties, ride a public bus, swim in a community pool. But that those activities may be in his future at all is extraordinary.

The treatment given to JaCeon is the result of decades of research into gene therapy that included a string of striking failures that led many doctors to abandon the pursuit altogether.

Gene therapy long had been considered a potential treatment for severe combined immunodeficiency disorder, or SCID, the condition JaCeon was born with, and some other genetic syndromes. The idea is to replace a single gene thats causing trouble.

Even as many doctors gave up on the promise of gene therapy, teams of stubborn scientists kept plugging away. And a few years ago, their experiments started to work, propelled by advances in the understanding of stem cells in this case, a type called hematopoietic stem cells that live in bone marrow and are responsible for generating blood and immune cells and improved methods of delivering genetic repairs.

JaCeon Golden is treated by patient care assistant Grace Deng (center) and pediatric oncology nurse Kat Wienskowski.

JaCeon Golden is treated by patient care assistant Grace Deng...

Now human gene therapy is being tested in trials at UCLA, where a team has treated 20 children with one type of SCID, and at UCSF in collaboration with St. Jude Childrens Research Hospital in Memphis. Both trials are funded by grants from the California Institute for Regenerative Medicine, the states stem cell agency, located in Oakland.

Researchers are studying similar therapies in hopes of curing genetic syndromes like sickle cell disease. And the stem cell agency is funding gene therapy research into potential treatments for HIV, brain cancer and Huntingtons disease, among others.

Gene therapy has been shown to work, the efficacy has been shown. And its safe, said Sohel Talib, a senior science officer at the state stem cell agency. The confidence has come. Now we have to follow it up.

JaCeon was born at a hospital in Las Cruces, N.M., and diagnosed with SCID just after birth as part of a standard newborn screening. He was flown to UCSF, one of a handful of facilities with expertise in SCID, when he was 3 weeks old. His great-aunt joined him about a month later, in November.

The immune disorder is commonly known as bubble baby disease, because until fairly recently kids born with it had to live in isolation, often in plastic bubbles in hospital rooms or their own homes to protect them from infections.

Babies born with SCID have a genetic mutation that leaves their immune system unable to develop disease-fighting cells. Without treatment, most will die within a year. Since the 1970s, some babies with SCID were cured with a bone-marrow transplant. But to be effective, a perfect match was required, almost always from a sibling, and only about a fifth of kids have such a match.

Ja'Ceon Golden is held by patient care assistant Grace Deng, as Deng bottle feeds Golden at UCSF Benioff Children's Hospital on Wednesday, March 8, 2017, in San Francisco, Calif. Golden, who is five months old, is diagnosed with severe combined immunodeficiency disease (SCID). He is a patient at UCSF, where he stays in a sterile room. The hospital is working on a new gene therapy treatment for SCID. Golden was brought from New Mexico for the experimental treatment.

Ja'Ceon Golden is held by patient care assistant Grace Deng, as...

The rest could undergo a bone marrow transplant from a partial match in JaCeons case, his great-aunt was one but even when that treatment was successful, kids were left with fragile immune systems that required constant maintenance with antibiotics and other boosts.

Gene therapy, though, may prove as effective as a bone marrow transplant from a perfect match.

The procedure starts with doctors harvesting stem cells from a babys own bone marrow, usually taken from the hip. In JaCeons case, his stem cells were sent in January to St. Jude in Memphis, where scientists are perfecting the gene-therapy delivery mechanism.

Sending away JaCeons stem cells was probably the most stressful time of my life, short of my own kids maybe being born, said Dr. Morton Cowan, the lead investigator of the UCSF trial, who has worked in SCID research for more than 30 years.

JaCeons stem cells were flown east over the first big weekend of major storms in California. Flights were being canceled around the clock, and doctors only had a window of about 36 hours to get the fresh cells to the labs in Memphis.

The trip was successful, but not without a hitch. After the cells were engineered and were being sent back to California, the material for a few heart-stopping hours got lost in the mail.

In a couple of months, Cowan said, he hopes to be able to do the gene-therapy delivery at UCSF labs, avoiding the travel headaches.

For now, that still happens at St. Jude. Doctors used a virus in fact, HIV, the virus that causes AIDS to deliver the gene therapy to JaCeons stem cells. The virus is neutered, with all of the disease-causing pieces inside removed.

Whats left is a missile-like shell designed to infiltrate a cell and deliver whatever payload doctors have inserted inside in this case, a healthy gene that will restore the stem cells ability to build normal immune cells.

Back in San Francisco, the cells were infused into JaCeon via a port in his chest. Because theyre his own cells, there was no fear his body would reject them.

He did have to undergo mild chemotherapy to kill off some of his own bone marrow and make room for the re-engineered stem cells to roost, but UCSF has been developing a technique for limiting the dosage of chemotherapy given in gene therapy procedures.

JaCeon suffered no obvious side effects from either the stem cell infusion or the chemotherapy drugs, doctors said.

Hes just thriving. Hes just hes great, Cowan said. He added, We cant open the Champagne just yet, but early tests show the new gene is active, and JaCeon has had an uptick of certain immune cells.

The infusion procedure took just 20 minutes, and JaCeon slept through it, but it felt momentous nonetheless.

It had been difficult to decide to enroll JaCeon in the trial, Hawkins said. Since she was a partial match for a bone marrow transplant, she had the option of giving him the traditional and well-tested therapy.

Shed said to his doctors, So youre telling me hes a guinea pig? They told her, she recalls, If it works, he can open the door for other kids.

That night, as Hawkins slept on the decision, I kept waking up, waking up, all night long, she said. If there was a possibility he could save someone else ... she added, and then broke off in tears.

She spends about six hours with JaCeon every day, beginning each morning with a bath in sterile water, brought by nurses in special tubs. Shes constantly wiping down his toys, clothes, bedding and stuffed animals.

Ive changed a lot of diapers in my time, but this is way more complicated than with other kids, Hawkins said, demonstrating the multistep process she uses to prevent diaper rash.

Im not going to say its been easy, she said. But hes doing fine. I wouldnt have it any other way.

Erin Allday is a San Francisco Chronicle staff writer. Email: eallday@sfchronicle.com

Twitter: @erinallday

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Amid advances in gene therapy, 'bubble baby' in SF gains hope - San Francisco Chronicle

The University of California, Davis, has reached a licensing agreement with Regenerative Arthritis and Bone Medicine (RABOME) for a class of drugs developed at the university that hold potential for treating diseases associated with bone loss and inflammatory arthritis.

From Left: Fred Tileston (RABOME), Ruiwu Liu, Nancy Lane, Christy Pifer, Wei Yao, Kit Lam (UC Davis Health), and Jiwei Chen (RABOME).

The license, negotiated by the InnovationAccess team within the UC Davis Office of Research, provides the university-affiliated startup with rights to four families of patents and patent applications related to the novel composition of a hybrid molecule, known as LLP2A-alendronate, which has been found to effectively direct mesenchymal stem cells (MSCs) to induce bone regeneration in animal models. The compound works by guiding transplanted and endogenous MSCs to the surface of the bone where they differentiate into bone-forming cells, thereby increasing bone mass and strength. These cells are also immune-modulating, which helps to reduce inflammation at target sites.

The use of stem cells as therapeutic agents is a growing field, but directing stem cells to travel and adhere to the surface of bone for bone formation has been an elusive goal in regenerative medicine.

There are many stem cells, even in elderly people, but they do not readily migrate to bone, said Wei Yao, co-inventor and associate professor of internal medicine at UC Davis. Finding a molecule that attaches to stem cells and guides them to the targets we need provides a real breakthrough.

Translating discovery into societal and commercial impact

Late last year, RABOME received approval from the U.S. Food and Drug Administration to begin phase I clinical trials to evaluate the safety of the drug in humans. The study sites are currently screening patients for enrollment.

We are pursuing several indications for use, but our initial focus is in developing a treatment for osteonecrosis, a disease caused by reduced blood flow to bones, says Fred Tileston, president and chief executive officer RABOME, which is a California-based company. As many as 20,000 people per year in the United States develop osteonecrosis.

RABOME also plans to pursue other indications for use including fracture healing, osteoporosis and inflammatory arthritis.

We are pleased that this very promising technology is being shepherded by Mr. Tileston, who is an experienced business leader and entrepreneur, said Dushyant Pathak, associate vice chancellor for Technology Management and Corporate Relations at UC Davis. It is exciting to see the teams progress in translating the discovery into commercial and societal impact.

Breaking barriers through cross-discipline collaboration

The development of the novel therapy is the result of a successful research collaboration between two teams at UC Davis: a group of experts on bone health, led by Nancy Lane and Wei Yao from the UC Davis Center for Musculoskeletal Health, and a synergistic group of medicinal chemists led by Kit Lam and Ruiwu Liu from the Department of Biochemistry and Molecular Medicine.

This research was a collaboration of stem cell biologists, biochemists, translational scientists, a bone biologist and clinicians, said Lane, endowed professor of medicine, rheumatology and aging research, anda principal investigator. It was a truly fruitful team effort with remarkable results.

Lane received a Disease Team Therapy Development research grant in 2012 from the California Institute for Regenerative Medicine (CIRM) which, along with federal grants from the National Institutes of Health, supported the preclinical research. CIRM was established in 2004 via California Proposition 71 to fund stem cell research in attempt to accelerate and improve treatments for patients where current needs are unmet.

Conflict of interest disclosure

Because Tileston and Lane are married, UC Davis conducted a conflict of interest review of its licensing agreement with RABOME. The university determined that it did not rise to the level of a financial conflict of interest under NIH rules, which require a finding of a direct and significant impact.

Send email Phone: 916-734-9048

AJ Chelin, Office of Research Send email Phone:530-752-1101

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UC Davis licenses novel compound that helps stem cells regenerate bone - HealthCanal.com (press release) (blog)

100+ Treatments In The Last Year Alone In Redding

This practice is dedicated to cutting edge, highly professional procurement and delivery of autologous mesenchymal stem cells. This field is exciting for us, as well as for our affiliated physicians, and being able to offer such innovative stem cell therapy is a privilege, though it comes with great responsibility.

The Northern California Stem Cell Treatment Center is partnered with a large global organization called Cell Surgical Network. This affiliation, involving over 50 centers worldwide, shares our passion for this work and allows our practice and our patients the ability to add consequentially to the scientific knowledge base in clinical stem cell treatments.

We are pleased to be able to utilize our over 90 years of combined experience and expertise in treating patients to help forge progress in this exciting type of medicine, and we are dedicated to safely delivering stem cell therapy to our patients. We've been treating patients in Redding for over a year and seen more than 100 cases come through our office.Though the advancements thus far have been phenomenal,we are on the cusp of even greater life-changing medical innovations.

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Northern California Stem Cell Treatment Center in Redding, CA

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by DAVID JENSEN posted 03.02.2017

The California stem cell agency this week approved nearly $33 million for clinical stage research projects testing treatments for type 1 diabetes, arthritis of the knee, ALS and an immunodeficiency affliction.

The awards were quickly approved with little discussion during a meeting at the Oakland headquarters of the California Institute for Regenerative Medicine or CIRM, as the agency is formally known.

The goal of the research is to regenerate knee cartilage through the use of a mesenchymal progenitor cell treatment, according to the agencys application review summary

The award likely to have an impact on the most people if it is successful is a relatively small, $2.3 million award to the Cellular Biomedicine Group, a Chinese firm with operations in Cupertino, Calif. The stem cell agency by law only finances work in Clifornia. The research would also be supported by $572,993 in co-funding.

The project is aimed at treating osteoarthritis of the knee. More than 51 million people in the United States suffer from arthritis, which is particularly common in the knee.

The goal of the research is to regenerate knee cartilage through the use of a mesenchymal progenitor cell treatment, according to the agencys application review summary. The funding would go to manufacture the product and complete work to secure Food and Drug Administration approval for a phase one safety trial. A treatment for the public would likely be years in the future.

Here are the other winners today of California stem cell cash with links to the summaries of the reviews.

Caladrius Biosciences of New Jersey won $12.2 million for a clinical trial for young people ages 12-17 for newly diagnosed type 1 diabetes. The firm plans to use regulatory T cells from the patients themselves to treat the disease. Caladrius has a California location in Mountain View. (Caladrius press release can be found here.)

St. Judes Research Hospital in Memphis, Tenn., was awarded $11.9 million for a phase one/two trial to treat infants with X-linked severe combined immunodeficiency. The trial would aim at enrolling at least six patients suffering from the catastrophic affliction. The treatment would use the patients own bone marrow stem cells after the cells were specially handled. The agency said in a press release that St. Judes is working with UC San Francisco. (St. Judes press release can be found here.)

The awards were previously approved behind closed doors by the agencys out-of-state reviewers, who do not disclose publicly their economic or professional interests.

Cedars-Sinai Medical Center in Los Angeles was awarded $6.2 million for a phase 1/2A trial to test a treatment for ALS, which has no treatment or cure. The CIRM review summary said a huge unmet need existed. About 20,000 persons in the United States suffer from the affliction.

CIRMs press release did not identify the researchers involved in any of the awards.

The agency is on a push to support more clinical trials, which are the last and most expensive research prior to the possibility of winning federal approval for widespread use of a therapy.

Currently the agency is participating in 27 trials and is planning on adding 37 more in the next 40 months. The agency is expected to run out of funds for new awards in June 2020 and has no source of future financing.

The awards were previously approved behind closed doors by the agencys out-of-state reviewers, who do not disclose publicly their economic or professional interests. The agencys directors rarely overturn a positive decision by the reviewers.

All of the winners have links to two or more members of the 29-member CIRM governing board. Those members are not allowed to vote on applications where they have conflicts of interest.

About 90 percent of the funds awarded by the board since 2005 have gone to institutions that have ties to members of the board, past or present, according to calculations by the California Stem Cell Report. Eds Note: David Jensen is a retired newsman who has followed the affairs of the $3 billion California stem cell agency since 2005 via his blog, the California Stem Cell Report, where this story first appeared. He has published more than 4,000 items on California stem cell matters in the past 11 years.

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Stem cell: Knee arthritis in new $33 million research plan - Capitol Weekly

Cellular Biomedicine Group Inc (NASDAQ: CBMG) is a micro-cap biomedicine company focused on the development of treatments for cancerous and degenerative diseases through cell-based technologies.

Last week, Benzinga attended SCN Corporate Connects Family Office & Life Science Symposium at the NASDAQ and had the chance to talk with CBMG CEO Tony Liu who walked us through some of the companys products, management team, market potential, how they use stem cells and more.

CBMG has two leading technology platforms at the time, Liu began. One is an immune cell therapy aimed at the treatment of a broad range of cancers using Cancer Vaccines, Chimeric Antigen Receptor T cell (CAR-T) and anti-PD-1 Technologies. The other one uses stem cells for regenerative purposes; the key indication for this therapy is knee osteoarthritis.

Our focus is on these technologies and our market is China, because that is the largest -by far- in population for the indication, he pointed out.

Benzinga: How does the company use stem cells.

Liu: In simple terms, a stem cell is basically regenerative. So a stem cell has the enormous power of expanding, continue from the embryonic stem cell to the baby stem cell and ultimately to the adult stem cell, so it has a great ability to continue to expand and grow.

From the medical perspective, an adult stem cell can regenerate, it can repair [tissue]. So, in our lead product, we use fat tissue from the stomach and we all have a few ounces of extra fat. We take the stem cell out from the fat tissue culture, expand it, and then we inject back in the kneecap for patients with a knee osteoarthritis problem.

Benzinga: Are there any other indications you will be targeting in the near-future?

Liu: Were targeting lymphoma, leukemia, solid tumors and many other areas.

Benzinga moved on to ask about the size of the market.

Liu: Every year we look at 4.5 million to 5 million new cancer patients. That is, every minute we are talking about eight or nine new cancer patients. That is why it is a huge social issue. That is one of the reasons why I choose to stay in the business after I spent 19 years with Microsoft Corporation (NASDAQ: MSFT) and four years with Alibaba Group Holding Ltd (NYSE: BABA). I think this area socially, you want to make impactful, and economically I think there is a huge business from that side.

Because our focus is on the Chinese market there are many investors in the U.S. who do not know us well. However, I believe investors should look at the company: we have a huge market, great scientists, manufacturing space

Then, for our stem cell therapies in China, 57 million people have a knee issue; in the U.S., 27 million [people] have a knee issue. Stem cells can help knees regenerate by doing two things. First, by helping with the pain, providing symptom relief and functional improvements. Secondly, they regenerate the cartilage, which originally caused the knee problem. Nowadays, patients can only opt between pain pills or a knee replacement.

Today, if you do a knee replacement, you are looking at tens of thousands [of dollars]. So, any way you look at it, [its a] multi-billion [market] for knee treatments.

Benzinga: When you say stem cells, people imagine It is a slightly controversial subject; it has some political implications. So, what is the Chinese governments stance regarding stem cells? Are there any risks? Is it accepted? What is the view of stem cells in China?

Liu: Chinas government has been extremely supportive of using stem cells. I think the controversy comes in where people use embryonic stem cells, when you create a new life, that is where the controversy is. But, we use what we call adult stem cells to improve peoples lives, improve their life experiences

On adult stem cells, there is little controversy. The policy of Chinas government is very clear. In fact, in the U.S. it is very clear as well. CBMG has been graced to work with the California Stem Cell Institute. Potentially, we are going to ask the U.S. for large-scale clinical trials.

Our management team was educated in the U.S., and has experience managing large businesses, Liu commented. Our Chief Scientific Officer is a former MedImmune/AstraZeneca plc (ADR) (NYSE: AZN) director. Some of our oncology scientists are from there as well. We also have scientists from the National Cancer Institute. We also have a person who is leading our manufacturing capabilities who worked for Harvard for 30 years and a top German company, leading research for seven years total.

So, we have this kind of people with skills come to China. Our company has 130 people with PhDs, and more than 30 with post-doctorate studies, so there is a lot of brain power, I believe, and we have a common vision that is to create the best, first in class, biotech business in China.

Benzinga: Whats one objective you have as a CEO for 2017?

Liu: In 2017 is about clinical, clinical, clinical. We now have moved our first two indications into the clinical trial stage. We have a lot of patients lined up for clinical trials.

So, as CEO Ill make sure we mobilize all the resources around the clinical trials and make sure we have the lead PI, lead hospitals, and we have resources waiting in the company to make sure we have successful clinical trials. Those are key elements, and we are confident that we should be able to move forward, given the number of patients we have, move schedule, look at the indications

Benzinga: Are you comfortable with your cash and debt position? Do you have any plans to raise capital this year or any time soon?

Liu: One of the benefits we have, CBMG has been regarded as the leader in Chinas cell therapy space, so we have investors who have given us money for the last three years, always at a premium to the market. They know who we are; they know the space we are in. I feel as we move forward, we will be getting more investment needs from trials, and I feel confident investors will look at CBMG as a way for them to both put money into the research, but also, as an investment that could reap great returns.

Benzinga: Your stock had been performing pretty well, but experienced a tumble between mid-November and late-February. What happened there?

Liu: CBMGs stock is really thinly traded. Much of the stock is owned by those who have been with the company for a long time; so, they dont sell. Having said this, there are many reasons that drive stocks: the U.S. election, the pricing discussion Many investors dont discriminate, and just punish biotech as a whole. However, CBMG is not really subject to most of these pricing pressures. In fact, because we have a different cost structure, I expect CBMG to do extremely well.

Image Credit: By Ryddragyn at English Wikipedia - Transferred fromen.wikipediato Commons., Public Domain, via Wikimedia Commons

Posted-In: Biotech News Emerging Markets Health Care Events Exclusives Markets Tech Best of Benzinga

2017 Benzinga.com. Benzinga does not provide investment advice. All rights reserved.

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Exclusive: CBMG CEO Talks Stem-Cell Therapies, Cancer Treatments, Financials & The Chinese Market - Benzinga

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SHANGHAI, China and CUPERTINO, Calif., Feb. 27, 2017 (GLOBE NEWSWIRE) Cellular Biomedicine Group Inc. (NASDAQ:CBMG)(CBMG or the Company), a clinical-stage biopharmaceutical firm engaged in the development of effective immunotherapies for cancer and stem cell therapies for degenerative diseases, announced today that the governing Board of the California Institute for Regenerative Medicine (CIRM), Californias stem cell agency, has awarded the Company $2.29 million to support pre-clinical studies of AlloJoinTM, CBMGs Off-the-Shelf Allogeneic Human Adipose-derived Mesenchymal Stem Cells for the treatment of Knee Osteoarthritis in the United States.

While CBMG recently commenced two Phase I human clinical trials in China using CAR-T to treat relapsed/refractory CD19+ B-cell Acute Lymphoblastic Leukemia (ALL) and Refractory Diffuse Large B-cell Lymphoma (DLBCL) as well as an ongoing Phase I trial in China for AlloJoinTM in Knee Osteoarthritis (KOA), this latest announcement represents CBMGs initial entrance into the United States for its off-the-shelf allogeneic stem cell candidate AlloJoinTM.

The $2.29 million was granted under the CIRM 2.0 program, a comprehensive collaborative initiative designed to accelerate the development of stem cell-based treatments for people with unmet medical needs. After the award, CIRM will be a more active partner with its recipients to further increase the likelihood of clinical success and help advance a pre-clinical applicants research along a funding pipeline towards clinical trials. CBMGs KOA pre-clinical program is considered late-stage, and therefore it meets CIRM 2.0s intent to accelerate support for clinical stage development for identified candidates of stem cell treatments that demonstrate scientific excellence.

We are deeply appreciative to CIRM for their support and validation of the therapeutic potential of our KOA therapy, said Tony (Bizuo) Liu, Chief Executive Officer of CBMG. We thank Dr. C. Thomas Vangsness, Jr., in the Department of Orthopaedic Surgery at the Keck School of Medicine of the University of Southern California and Dr. Qing Liu-Michael at the Broad Center for Regenerative Medicine and Stem Cell Research at USC, who helped significantly with the grant application process. The CIRM grant is the first step in bringing our allogeneic human adipose-derived mesenchymal stem cell treatment for knee osteoarthritis (AlloJoinTM) to the U.S. market.

Our AlloJoinTM program has previously undergone extensive manufacturing development and pre-clinical studies and is undergoing a Phase I clinical trial in China. In order to demonstrate comparability with cell banks previously produced in China for our U.S. IND filing, we are addressing the pre-clinical answers required for the FDA. With the funds provided by CIRM, we will replicate and validate the manufacturing process and control system at the cGMP facility located at Childrens Hospital Los Angeles to support the filing of an IND with the FDA. The outcome of this grant will enable us to have qualified final cell products ready to use in a Phase I clinical trial with Dr. Vangsness as the Principal Investigator and the Keck School of Medicine of USC as a trial site. Dr. Vangsness is familiar with both stem cell biology and KOA, and has led the only randomized double-blind human clinical study to investigate expanded allogeneic mesenchymal stem cells to date. Our endeavor in the U.S. market will further strengthen our commercialization pipeline.

CBMG recently announced promising interim 3-month safety data from its Phase I clinical trial in China for AlloJoinTM, its off-the-shelf allogeneic stem cell therapy for KOA. The trial is on schedule to be completed by the third quarter of 2017.

About CIRM

At CIRM, we never forget that we were created by the people of California to accelerate stem cell treatments to patients with unmet medical needs, and to act with a sense of urgency commensurate with that mission. To meet this challenge, our team of highly trained and experienced professionals actively partners with both academia and industry in a hands-on, entrepreneurial environment to fast track the development of todays most promising stem cell technologies.

With $3 billion in funding and over 280 active stem cell programs in our portfolio, CIRM is the worlds largest institution dedicated to helping people by bringing the future of medicine closer to reality.

For more information, please visit http://www.cirm.ca.gov.

About Knee Osteoarthritis

According to the Foundation for the National Institutes of Health, there are 27 million Americans with Osteoarthritis (OA), and symptomatic Knee Osteoarthritis (KOA) occurs in 13% of persons aged 60 and older. The International Journal of Rheumatic Diseases, 2011 reports that approximately 57 million people in China suffer from KOA. Currently no treatment exists that can effectively preserve knee joint cartilage or slow the progression of KOA. Current common drug-based methods of management, including anti-inflammatory medications (NSAIDs), only relieve symptoms and carry the risk of side effects. Patients with KOA suffer from compromised mobility, leading to sedentary lifestyles; doubling the risk of cardiovascular diseases, diabetes, and obesity; and increasing the risk of all causes of mortality, colon cancer, high blood pressure, osteoporosis, lipid disorders, depression and anxiety. According to the Epidemiology of Rheumatic Disease (Silman AJ, Hochberg MC. Oxford Univ. Press, 1993:257), 53% of patients with KOA will eventually become disabled.

About Cellular Biomedicine Group (CBMG)

Cellular Biomedicine Group, Inc. develops proprietary cell therapies for the treatment of cancer and degenerative diseases. Our immuno-oncology and stem cell projects are the result of research and development by CBMGs scientists and clinicians from both China and the United States. Our GMP facilities in China, consisting of twelve independent cell production lines, are designed and managed according to both China and U.S. GMP standards. To learn more about CBMG, please visit http://www.cellbiomedgroup.com.

Forward-looking Statements

This press release contains forward-looking statementsincluding descriptions of plans, strategies, trends, specific activities, investments and other non-historical factsas defined by the Private Securities Litigation Reform Act of 1995, Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking information is inherently uncertain, and actual results could differ materially from those anticipated due to a number of factors, which include risks inherent in doing business, trends affecting the global economy (including the devaluation of the RMB by China in August 2015), and other risks detailed in CBMGs reports filed with the Securities and Exchange Commission, quarterly reports on form 10-Q, current reports on form 8-K and annual reports on form 10-K. Forward-looking statements may be identified by terms such as may, will, expects, plans, intends, estimates, potential, continue or similar terms or their negations. Although CBMG believes the expectations reflected in the forward-looking statements are reasonable, they cannot guarantee that future results, levels of activity, performance or achievements will be obtained. CBMG does not have any obligation to update these forward-looking statements other than as required by law.

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Cellular Biomedicine Group Awarded $2.29 Million Grant from the California Institute for Regenerative Medicine (CIRM) - OrthoSpineNews

Infants born with a type of the devastating immune disorder SCID, or bubble boy disease, may have the option of a novel gene therapy treatment, thanks to a clinical trial atUCSF Benioff Childrens Hospital San Francisco.

The trial is funded by a five-year, $11.9-million grant from theCalifornia Institute for Regenerative Medicine (CIRM)to test technology developed by St. Jude Childrens Research Hospital that delivers a functional gene into the patients blood-producing stem cells. If successful, the gene therapy could provide an alternative to stem cell transplants using donor cells, which can result in serious infection.

The trial expects to treat up to 15 children over the next five years and is open to patients with X-linked severe combined immunodeficiency disease (X-linked SCID), which affects only males. This is the most common form of SCID, which occurs in 1 in every 60,000 newborns, and is caused by defects in the functioning of lymphocytes the white blood cells that are the advanced fighting forces of the immune system. Babies born with SCID appear normal at birth but become sick from infections, skin rashes and failure to gain weight at 3-to-6 months of age. Without a stem cell transplant, they may die before their first birthday.

What is unique about this trial is that the patients own bone marrow stem cells are collected and corrected with the gene therapy, and the corrected cells are then reinfused into the patient, saidMorton Cowan, M.D., of theUCSF Division of Allergy, Immunology, and Blood and Marrow Transplant, and principal investigator of the trial at UCSF.

In stem cell transplants from a donor other than the patient, up to 20 percent of patients with SCID will develop graft-versus-host disease, in which the donor cells attack the recipients tissues. In addition, there is always a risk of the recipient rejecting the donor cells, Cowan said. Using the patients own stem cells means no rejection and no graft-versus-host disease.

The bone marrow transplant program at UCSF is among the largest SCID transplant centers in North America. UCSF pediatric immunologistJennifer Puck, M.D., is known for pioneering the SCID screening method and for nominating SCID to a federal advisory committee for inclusion in the newborn screening panel. Since the screen became available in California in 2010, UCSF has treated more than 30 infants diagnosed with SCID by newborn screening.

UCSF also played an instrumental role in the St. Jude treatment protocol by including a targeted chemotherapy agent, busulfan, along with the gene therapy, which is expected to optimize immune correction. While previous trials have tested gene therapy for this condition, they did not combine it with chemotherapy and had only partial immune correction. Since a low dose of the medication is used, short- and long-term effects are expected to be minimized.

Three patients already have been treated with this lentiviral gene therapy vector two at St. Jude and one at UCSF. The transduction process, in which genetic material is transferred via vector, currently takes place at St. Jude, which freezes the transduced cells and returns them to UCSF for infusion into the patient. The CIRM funding will enable UCSF to begin doing transductions using the St. Jude vector at theUCSF Pediatric Cell Therapy Laboratory, as well as covering the cost of treating patients in the trial.

We believe this trial will not only help us understand more about how lentiviral gene therapy works, but how the use of low-dose busulfan potentially will be effective in treating other non-malignant diseases like sickle-cell anemia, chronic granulomatous disease, marrow failure syndromes and even some cancers in which the patient is too ill to undergo the more toxic traditional treatments, said Cowan.

It will also give us a better idea of what toxicities may be associated with the use of these new vectors, in particular whether they are indeed safer than the older, gamma-retroviral vectors that were associated with a high risk of leukemia, seen in early gene therapy trials for X-linked SCID and other primary immune deficiencies.

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Gene therapy offers hope for newborns with severe immune disorder - University of California

TEMPE, Ariz. On the day he hoped would save his elbow, Garrett Richards laid face down on a table with his back exposed. A doctor guided a needle into the iliac crest of his pelvic bone and began to extract bone marrow. Richards was wide awake, the blessing of local anesthesia saving him from physical pain but not the anxiety that crept into his head: Is this really going to work?

Within a few minutes, the harvested marrow was hurried to a centrifuge, spun to separate the good stuff, mixed into a slurry of platelet-rich plasma and readied to inject into Richards damaged right elbow. Rather than the standard tear across his ulnar collateral ligament, Richards ran lengthwise along the middle of his UCL, a rare manifestation of an increasingly commonplace injury that almost always ends with Tommy John surgery. Not in this case. While he could have chosen that route, he wanted to explore first the efficacy of the aforementioned good stuff: stem cells.

Today, Garrett Richards is darting 98-mph fastballs again. I feel as good as I ever have throwing a baseball, he said Monday from Tempe Diablo Stadium, where the Los Angeles Angels, perhaps the most Tommy John-addled team in baseball, expect to break camp with Richards as their opening day starter. The 28-year-old is the latest player to turn to orthobiologics, the class of treatments that includes stem cells and PRP, in hopes of healing an injury. While clinical studies have shown great success with those who use orthobiologics, they are not yet a panacea for the pervasive elbow injuries in baseball for two reasons: They work only on partial ligament tears, like Richards, and medical studies have yet to validate their efficacy independent of other treatments run concurrently.

The lack of knowledge as to how orthobiologics work inside the body while the proteins in stem cells and platelets are believed to regrow damaged tissue, doctors have yet to isolate best practices for particular injuries speaks to the difficulties in true medical advances. Still, the desire of Richards and others to avoid surgery lends orthobiologics enough credence to warrant further studies.

I truly think this kind of treatment has significant potential, said Dr. Neal ElAttrache, a longtime orthopedic surgeon at the Kerlan-Jobe clinic in Los Angeles who introduced orthobiologics to Major League Baseball when he injected PRP into the elbow of Dodgers reliever Takashi Saito in 2008. Theres no question biologics are here to stay and biologic manipulation is the frontier of treatment in what were doing. The problem, as I see it, is that the marketing and clinical use has far exceeded the science behind it.

Translation: Once the use of PRP and stem cells found traction in the media, pro athletes and weekend warriors alike sought their use, even if the success stories skewed anecdotal. Bartolo Colon resurrected his career after a stem cell injection in 2010 and is still pitching today at 43. Others did so without the fanfare or publicity. Richards faced a choice after being diagnosed with a partially torn UCL last May: Undergo Tommy John surgery and, at earliest, return following the 2017 All-Star break or follow the advice of Dr. Steve Yoon, a partner of ElAttraches at Kerlan-Jobe, and try to salvage the ligament with stem cells.

Science, bro, Richards said. Im a believer now.

Two weeks before Richards began his treatment, teammate Andrew Heaney had looked to avoid Tommy John via stem cells. Richards figured theyd rehab together every step of the way and be back in time for the fall instructional league. Then at the end of June, a scan showed Heaneys elbow wasnt healing, and he would need reconstructive surgery. Already Tyler Skaggs had taken nearly two years to return from his 2014 surgery, and six weeks after Heaneys, starter Nick Tropeano went down. Like Heaney, he is expected to miss the 2017 season.

It made Richards recovery that much more imperative. His first checkup, six weeks in, showed regrowth in the torn area via ultrasound. By August, he started throwing, and come October, when instructional league was in full bloom, so too was Richards. He didnt hesitate to pump his fastball and rip off one of his spin-heavy breaking balls. As far as pure, raw stuff goes, few in baseball can match Richards.

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He was convinced science was working, bro, though the skepticism about orthobiologics generally remains, and understandably so, in the medical community. In May 2013, a paper published in the American Journal of Sports Medicine found 30 of 34 overhand throwers with partial UCL tears who used PRP had returned to their previous level of competition. This was reason for celebration. If a player could avoid the 14-month-plus recovery from the surgery, better for him as well as the team.

Another study arrived in 2016 that didnt cast doubt on the value of orthobiologics so much as offer a different avenue: rest. The 28 players used everything from electrical stimulation, ultrasound, laser therapy, massage and other soft-tissue work. And when paired with rest, their return to previous level came in at 84 percent. It was almost exactly as effective as PRP.

This reinforced ElAttraches concern: Neither of those studies had a control group against which to measure, so the numbers, while impressive, could not isolate what helped and what didnt. This chicken-or-egg question struck ElAttrache just the same when Saito returned and went on to pitch five seasons.

Maybe it was the injection, ElAttrache said. Or maybe it was that we shut him down and let him heal.

Garrett Richards is darting 98-mph fastballs again after turning to orthobiologics. (Getty Images)

He doesnt know, and thats an important distinction as orthobiologics grows exponentially. In 2004, voters in California pledged to provide $3 billion for stem-cell research and create the California Institute of Regenerative Medicine. It remains a benefactor for an industry trying to find its place in the United States.

Across the world, stem cells have far greater potency. U.S. law prevents doctors from manipulating the cells in any way. They are extracted and put back into patients bodies as is. In Switzerland, for example, doctors will harvest stem cells, manipulate them to promote greater healing capacity and then inject them. At least one star pitcher this offseason sought a stem cell injection in the United States, according to sources, while another veteran traveled halfway across the world to Zurich, seeking the comparative lack of regulations just as Peyton Manning did in 2011 to help heal a neck injury that eventually needed surgery.

The future of orthobiologics domestically doesnt end with the FDA loosening rules on stem cell usage. Doctors see significant promise in stem cells from a babys umbilical cord or a mothers placenta, both of which can be frozen. Already theyre capable of harvesting stem cells from old patients and engineering the cells into an immature state. The possibilities going forward are endless.

For right now, theyre going to play themselves out in Anaheim. The danger zone for re-injury after using orthobiologics tends to fall between April and June, though Richards cant imagine falling prey again. In addition to the 13-week break from throwing he took over the summer, Richards spent 10 more weeks in the offseason letting it heal further.

During his down time, Richards studied his own delivery to find even the slightest inefficiencies. He had three numbers in mind. The first was 85. Thats the percent at which he said hell throw his fastball, though because of improved mechanics he expects it wont hinder his velocity. The second is 100. Thats the pitch limit the Angels will foist on Richards, and hes not one to fight. The third is 200. Thats the number of innings Richards wants to pitch this season. He did it in 2015 and sees no reason he cant again.

If he can throw 85 percent, keep his pitch count below 100 and get those 200 innings, it will play publicly as another validation of orthobiologics. Just the same, if Richards elbow gives out eventually, his association with stem cells could perhaps give those considering it pause. Richards pays no mind to this. He just wants to be great.

So much so, in fact, that its going to cost him. Inside the Angels clubhouse, a chart, labeled 1 through 13, is taped to the side of a locker. Its a list of shame with the price buying lunch for the entire team. Players, coaches, P.R. directors, even manager Mike Scioscia are on there. Next to No. 6, it read: G. Rich Ace. He had made the mistake of saying aloud what he believed to be true: that hes the ace of the Angels.

Fulfilling that depends on plenty of things, none as important as his elbow, and Richards knows that. Hell do everything he can to take care of it, to nurture it, to fight against its natural gift of velocity that puts him at such risk. To make sure that next time hes on a table in the doctors office, its not with his elbow opened up and another season lost.

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How baseball players are trying stem cells to avoid Tommy John - Yahoo Sports

Americans spend between one and four billion dollars a year treating hair loss.

Now, four surgeons in the U.S. are testing a stem cell treatment in a non-surgical procedure.

Overseas trials in Japan and Egypt are already showing some success.

Its been 30 years of concern, Roy Woelke said.

Woelke knows how overwhelming hair loss can be.

I noticed thinning in my late twenties, and it never stops. It seems like it just goes on and on, Woelke detailed.

Hes had three hair replacement surgeries, but thats really just moving hair around the head, and as he says, you run out of supply.

Kenneth Williams, D.O., a hair restoration surgeon at Orange County Hair Restoration in Los Angeles, California, may have new hope for Woelke and millions of others.

Hes running a clinical trial that uses stem cells and platelet-rich plasma, or PRP, to treat baldness.

The study is taking cells that are in our body that help to regenerate or stimulate inactive or dormant hair follicles," Williams explained. "That is the theory behind what were doing this procedure on.

Williams takes fat from the abdomen, emulsifies it and separates the stem cells, mixes it with the patients own plasma which has been spun down to be super concentrated. Then with 300 shots, injects the mixture into the scalp, twice over a three-month period.

Woelke hopes to get into the trial, which has five participants so far.

Williams already does the procedure for paying patients whove had promising results.

Those patients are seeing some differences in the density of the hair," Williams said. "Were waiting for the final results, which take nine to 12 months after the administration. We look to see the final results of what were doing.

He hopes to publish results in two years.

Williams trial is supported by NIH, but not by a major pharmaceutical company yet. That means his trial is patient-funded, meaning theyll pay a reduced cost of the $2,500 to $5,800 procedure, depending on which arm of the trial is chosen.

Contact the Irvine Institute of Medicine and Cosmetic Surgery at (949) 333-2999 or visit http://www.straandstudy.com for more information.

Published at 5:46 PM CST on Feb 17, 2017 | Updated at 5:50 PM CST on Feb 17, 2017

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Stem Cells Treat Baldness with PRP | NBC 5 Dallas-Fort Worth - NBC 5 Dallas-Fort Worth