June 5, 2014

Nathan Hurst, University of Missouri

One of the biggest challenges for medical researchers studying the effectiveness of stem cell therapies is that transplants or grafts of cells are often rejected by the hosts. This rejection can render experiments useless, making research into potentially life-saving treatments a long and difficult process. Now, researchers at the University of Missouri have shown that a new line of genetically modified pigs will host transplanted cells without the risk of rejection.

The rejection of transplants and grafts by host bodies is a huge hurdle for medical researchers, said R. Michael Roberts, Curators Professor of Animal Science and Biochemistry and a researcher in the Bond Life Sciences Center. By establishing that these pigs will support transplants without the fear of rejection, we can move stem cell therapy research forward at a quicker pace.

In a published study, the team of researchers implanted human pluripotent stem cells in a special line of pigs developed by Randall Prather, an MU Curators Professor of reproductive physiology. Prather specifically created the pigs with immune systems that allow the pigs to accept all transplants or grafts without rejection. Once the scientists implanted the cells, the pigs did not reject the stem cells and the cells thrived. Prather says achieving this success with pigs is notable because pigs are much closer to humans than many other test animals.

Many medical researchers prefer conducting studies with pigs because they are more anatomically similar to humans than other animals, such as mice and rats, Prather said. Physically, pigs are much closer to the size and scale of humans than other animals, and they respond to health threats similarly. This means that research in pigs is more likely to have results similar to those in humans for many different tests and treatments.

Now that we know that human stem cells can thrive in these pigs, a door has been opened for new and exciting research by scientists around the world, Roberts said. Hopefully this means that we are one step closer to therapies and treatments for a number of debilitating human diseases.

Roberts and Prather published their study, Engraftment of human iPS cells and allogeneic porcine cells into pigs with inactivated RAG2 and accompanying severe combined immunodeficiency in the Proceedings of the National Academy of Sciences.

Source: Nathan Hurst, University of Missouri

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Stem Cells Successfully Transplanted And Grown In Pigs

ALAMEDA, Calif.--(BUSINESS WIRE)--BioTime, Inc. (NYSE MKT: BTX) and its subsidiary Asterias Biotherapeutics, Inc. today announced that Jane S. Lebkowski, PhD, President, Research & Development of Asterias, will present at the 17th Annual Meeting of the American Society of Gene & Cell Therapy taking place May 20-24, 2014 in Washington, DC.

Dr. Lebkowskis presentation will take place in the session titled The Next Generation in Stem Cell Therapies on Thursday May 22, 2014 at 10:15 AM EDT at the Marriot Wardman Park, Washington, DC. Dr. Lebkowskis presentation is titled Phase I Clinical Trial of Human Embryonic Stem Cell-Derived Oligodendrocyte Progenitors in Patients with Neurologically Complete Thoracic Spinal Cord Injury: Results and Next Steps. In her presentation, Dr. Lebkowski will disclose for the first time certain Phase I clinical trial results of OPC1. The presentation will be made available on BioTimes and Asterias websites at http://www.biotimeinc.com and http://www.biotimeinc.com/asterias-biotherapeutics/.

About Asterias

Asterias is a biotechnology company focused on the emerging field of regenerative medicine. Our core technologies center on stem cells capable of becoming all of the cell types in the human body, a property called pluripotency. We plan to develop therapies based on pluripotent stem cells to treat diseases or injuries in a variety of medical fields, with an initial focus on the therapeutic applications of oligodendrocyte progenitor cells (OPC1) and antigen-presenting dendritic cells (VAC1 and VAC2) for the fields of neurology and oncology respectively. OPC1 was tested for treatment of spinal cord injury in the worlds first Phase 1 clinical trial using human embryonic stem cell-derived cells. We plan to reinitiate clinical testing of OPC1 in spinal cord injury this year, and are also evaluating its function in nonclinical models of multiple sclerosis and stroke. VAC1 and VAC2 are dendritic cell-based vaccines designed to immunize cancer patients against the telomerase, a protein abnormally expressed in over 95% of human cancer types. VAC2 differs from VAC1 in that the dendritic cells presenting telomerase to the immune system are produced from human embryonic stem cells instead of being derived from human blood.

In October of 2013, Asterias acquired the cell therapy assets of Geron Corporation. These assets included INDs for the clinical stage OPC1 and VAC1 programs, banks of cGMP-manufactured OPC1 drug product, cGMP master and working cell banks of human embryonic stem cells, over 400 patents and patent applications filed worldwide, research cell banks, customized reagents and equipment, and various assets relating to preclinical programs in cardiology, orthopedics, and diabetes.

Asterias is a member of the BioTime family of companies.

About BioTime

BioTime is a biotechnology company engaged in research and product development in the field of regenerative medicine. Regenerative medicine refers to therapies based on stem cell technology that are designed to rebuild cell and tissue function lost due to degenerative disease or injury. BioTimes focus is on pluripotent stem cell technology based on human embryonic stem (hES) cells and induced pluripotent stem (iPS) cells. hES and iPS cells provide a means of manufacturing every cell type in the human body and therefore show considerable promise for the development of a number of new therapeutic products. BioTimes therapeutic and research products include a wide array of proprietary PureStem progenitors, HyStem hydrogels, culture media, and differentiation kits. BioTime is developing Renevia (a HyStem product) as a biocompatible, implantable hyaluronan and collagen-based matrix for cell delivery in human clinical applications. In addition, BioTime has developed Hextend, a blood plasma volume expander for use in surgery, emergency trauma treatment and other applications. Hextend is manufactured and distributed in the U.S. by Hospira, Inc. and in South Korea by CJ HealthCare Corporation under exclusive licensing agreements.

BioTime is also developing stem cell and other products for research, therapeutic, and diagnostic use through its subsidiaries:

Additional information about BioTime can be found on the web at http://www.biotimeinc.com.

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Asterias Biotherapeutics, Inc. to Present Phase I Clinical Data at the 17th Annual Meeting of the American Society of ...

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Newswise CAMBRIDGE, Mass. (May 15, 2014) By studying nerve and liver cells grown from patient-derived induced pluripotent stem cells (iPSCs), Whitehead Institute researchers have identified a potential dual-pronged approach to treating Niemann-Pick type C (NPC) disease, a rare but devastating genetic disorder.

According to the National Institutes of Health (NIH), approximately 1 in 150,000 children born are afflicted with NPC, the most common variant of Niemann-Pick. Children with NPC experience abnormal accumulation of cholesterol in their liver and nerve cells, leading to liver failure, neurodegeneration, andultimatelydeath, often before age 10.

Although there is currently no effective treatment for NPC disease, a clinical trial examining potential cholesterol-lowering effects of the drug cyclodextrin in NPC patients is ongoing. However, research in Whitehead Founding Member Rudolf Jaenischs lab led by Dorothea Matezel along with Sovan Sarkar suggests that the high doses may actually be harmful. This and other findings are reported this week in the journal Stem Cell Reports.

At those levels of cyclodextrin (in the clinical trial), Maetzel and her coauthors show that cells encounter a further block in autophagy that could be detrimental, says Jaenisch, who is also a professor of biology at Massachusetts Institute of Technology. But when they use it at a lower dose in combination with another small molecule, carbamazepine, which stimulates autophagy, then it significantly improves the survival of the cells. Such an approach lowers cholesterol levels and restores the autophagy defects at the same time. This could be a new type of treatment for NPC disease.

To clarify what is amiss in NPC and identify potential therapeutics that could correct these problems, Maetzel generated iPSCs from patients with the most common genetic mutation that causes NPC. She created the iPSCs by pushing skin cells donated by the patients back to an embryonic stem cell-like state. These iPSCs were differentiated into liver and neuronal cells, the cell types most affected in NPC. Along with Haoyi Wang, a postdoctoral researcher in the Jaenisch lab, she then corrected one copy of the causal mutation, in the NPC1 gene, to create control cells whose genomes differ only at the single edited gene copy.

When Maetzel and Sarkar analyzed the cellular functions in the NPC1-mutant and control cell lines, they determined that although cholesterol does build up in the NPC1-mutant cells, a more significant problem is defective autophagya basic cellular function that degrades and recycles unneeded or faulty molecules, components, or organelles in a cell. The impaired autophagy prevents normal elimination of its cargo, such as damaged organelles or other substrates like p62, which then accumulates and damages the cells. The finding confirms previous work from the Jaenisch lab linking the NPC1 mutation to defective autophagy in mouse cells.

Autophagy dysfunction has major implications in several neurodegenerative and certain liver conditions, and therefore autophagy modulators have tremendous biomedical relevance, says Sarkar. We wanted to screen for compounds stimulating autophagy in human disease-relevant cells and show the beneficial effects of such an approach in the context of a lipid/lysosomal storage disorder.

Maetzel and Sarkar used the two types of human disease-affected cells to screen for compounds known to improve autophagy but not impacting on the mammalian target of rapamycin (mTOR) pathway, which has critical cellular functions and also controls autophagy. They found only one capable of jumpstarting autophagy independently of mTOR in both liver and nerve cells. When this drug, carbamazepine, which is a mood stabilizer prescribed for bipolar disorder, was added in combination with low doses of cyclodextrin, both cholesterol accumulation and autophagy defects were rescued in the NPC-mutated cells.

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Combination Therapy a Potential Strategy for Treating Niemann Pick Disease

BioTimes efforts in the first quarter of 2014 were focused on advancing near-term products through clinical trials while also preparing certain novel stem cell-based therapeutics for clinical trials later this year. Enrollment in three diagnostic clinical studies has remained rapid, with completion expected later in 2014. Following the successful safety trial of ReneviaTM, we have made rapid progress in preparing for the pivotal ReneviaTM trial during the second half of the year, said Michael D. West, Ph.D., BioTimes Chief Executive Officer. At our subsidiary Asterias Biotherapeutics, we have been preparing to initiate a new Phase 1/2a clinical trial of OPC1 for the treatment of spinal cord injury in 2014, pending clearance from the FDA, and also preparing our VAC2 cancer vaccine for a potential clinical trial. Also in the quarter, BioTimes subsidiary Cell Cure Neurosciences Ltd. advanced preclinical development of OpRegen for a planned IND filing in 2014 for the treatment of age-related macular degeneration.

We have continued to develop our subsidiaries businesses, commented Dr. West. Shares of the Series A common stock of our subsidiary Asterias Biotherapeutics, Inc. are now scheduled to begin trading publicly this summer following Gerons distribution of those shares to its stockholders, for which a record date of May 28th has been set. We were also pleased to recently announce that LifeMap Solutions, Inc., a newly organized subsidiary of our LifeMap Sciences, Inc., has entered into an agreement with a major medical center to create innovative mobile health (mHealth) products powered by biomedical and other personal big data.

As the industry leader in regenerative medicine with over 600 patents and patent applications worldwide, BioTime and its subsidiaries have assembled a broad array of strategically important regenerative medicine technologies and assets for the development of therapeutic and diagnostic products, Dr. West continued. Our expenditure levels were higher than usual during the fourth quarter and the recently ended first quarter, but our recent progress in streamlining our workforce through shared core resources among our subsidiaries should reduce our cash burn rate and optimize value for our shareholders during this exciting time in the companys history. We would like to thank our long-term investors for their continued support and our collaborators at leading academic medical institutions for their help in advancing our products toward our goal of helping patients who have serious unmet medical needs.

First Quarter and Recent Highlighted Corporate Accomplishments

Financial Results

Revenue

For the quarter ended March 31, 2014, on a consolidated basis, total revenue was $1.1 million, up $0.5 million from $0.6 million for the same period one year ago. The increase in first quarter revenue is primarily attributable to grant income awarded to BioTimes subsidiary Cell Cure Neurosciences Ltd. from Israels Office of the Chief Scientist.

Expenses

Operating expenses for the three months ended March 31, 2014 were $12.1 million, compared to expenses of $8.8 million for the same period of 2013. The increase in operating expenses is primarily attributable to an increase in staffing and the expansion of research and development efforts of Asterias and the amortization expense of intangible assets recorded in connection with the Geron stem cell asset acquisition in October 2013.

Net Loss

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BioTime Announces First Quarter 2014 Results and Recent Developments

New York, NY (PRWEB) April 29, 2014

The Stem Cell Institute located in Panama City, Panama, welcomes special guest speaker Roberta F. Shapiro, DO, FAAPM&R to its public seminar on umbilical cord stem cell therapy on Saturday, May 17, 2014 in New York City at the New York Hilton Midtown from 1:00 pm to 4:00 pm.

Dr. Shapiro will discuss A New York Doctors Path to Panama.

Dr. Shapiro operates a private practice for physical medicine and rehabilitation in New York City. Her primary professional activities include outpatient practice focused on comprehensive treatment of acute and chronic musculoskeletal and myofascial pain syndromes using manipulation techniques, trigger point injections, tendon injections, bursae injections, nerve and motor point blocks. Secondary work at her practice focuses on the management of pediatric onset disability.

She is the founder and president of the Dayniah Fund, a non-profit charitable foundation formed to support persons with progressive debilitating diseases who are faced with catastrophic events such as surgery or illness. The Dayniah Fund educates the public about the challenges of people with disabilities and supports research on reducing the pain and suffering caused by disabling diseases and conditions.

Dr. Shapiro serves as assistant clinical professor in the Department of Rehabilitation and Regenerative Medicine at Columbia University Medical Center.

Stem Cell Institute Speakers include:

Neil Riordan PhD Clinical Trials: Umbilical Cord Mesenchymal Stem Cell Therapy for Autism and Spinal Cord Injury

Dr. Riordan is the founder of the Stem Cell Institute and Medistem Panama Inc.

Jorge Paz-Rodriguez MD Stem Cell Therapy for Autoimmune Disease: MS, Rheumatoid Arthritis and Lupus

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department IPS Cell Therapy IPS Cell Therapy

For the first time, cloning technologies have been used to generate stem cells that are genetically matched to adult patients.

Fear not: No legitimate scientist is in the business of cloning humans. But cloned embryos can be used as a source for stem cells that match a patient and can produce any cell type in that person.

Researchers in two studies published this month have created human embryos for this purpose. Usually an embryo forms when sperm fertilizes egg; in this case, scientists put the nucleus of an adult skin cell inside an egg, and that reconstructed egg went through the initial stages of embryonic development.

This is a dream that weve had for 15 years or so in the stem cell field, said John Gearhart, director of the Institute for Regenerative Medicine at the University of Pennsylvania. Gearhart first proposed this approach for patient-specific stem cell generation in the 1990s but was not involved in the recent studies.

Stem cells have the potential to develop into any kind of tissue in the human body. From growing organs to treating diabetes, many future medical advances are hoped to arise from stem cells.

Scientists wrote in the journal Cell Stem Cell this month that they used skin cells from a man, 35, and another man, 75, to create stem cells from cloned embryos.

We reaffirmed that it is possible to produce patient-specific stem cells using a nuclear transfer technology regardless of the patients age, said co-lead author Young Gie Chung at the CHA Stem Cell Institute in Seoul, South Korea.

On Monday, an independent group led by scientists at the New York Stem Cell Foundation Research Institute published results in Nature using a similar approach. They used skin cells from a 32-year-old woman with Type 1 diabetes to generate stem cells matched to her.

Both new reports follow the groundbreaking research published last year by Shoukhrat Mitalipov and colleagues at Oregon Health & Science University in the journal Cell. In that study, researchers produced cloned embryos and stem cells using skin cells from a fetus and an 8-month-old baby.

Its a remarkable process that gives us these master cells, these stems cells that are essentially the seeds for all of the tissues in our bodies, said George Daley, director of the Stem Cell Transplantation Program at Boston Childrens Hospital, who was not involved in the recent studies. Thats why its so important for medical research.

Read more here:
Cloning used to make stem cells from adult humans

For the first time, cloning technologies have been used to generate stem cells that are genetically matched to adult patients.

Fear not: No legitimate scientist is in the business of cloning humans. But cloned embryos can be used as a source for stem cells that match a patient and can produce any cell type in that person.

Researchers in two studies published this month have created human embryos for this purpose. Usually an embryo forms when sperm fertilizes egg; in this case, scientists put the nucleus of an adult skin cell inside an egg, and that reconstructed egg went through the initial stages of embryonic development.

"This is a dream that we've had for 15 years or so in the stem cell field," said John Gearhart, director of the Institute for Regenerative Medicine at the University of Pennsylvania. Gearhart first proposed this approach for patient-specific stem cell generation in the 1990s but was not involved in the recent studies.

Stem cells have the potential to develop into any kind of tissue in the human body. From growing organs to treating diabetes, many future medical advances are hoped to arise from stem cells.

Scientists wrote in the journal Cell Stem Cell this month that they used skin cells from a man, 35, and another man, 75, to create stem cells from cloned embryos.

"We reaffirmed that it is possible to produce patient-specific stem cells using a nuclear transfer technology regardless of the patient's age," said co-lead author Young Gie Chung at the CHA Stem Cell Institute in Seoul, South Korea.

On Monday, an independent group led by scientists at the New York Stem Cell Foundation Research Institute published results in Nature using a similar approach. They used skin cells from a 32-year-old woman with Type 1 diabetes to generate stem cells matched to her.

Both new reports follow the groundbreaking research published last year by Shoukhrat Mitalipov and colleagues at Oregon Health & Science University in the journal Cell. In that study, researchers produced cloned embryos and stem cells using skin cells from a fetus and an 8-month-old baby.

"It's a remarkable process that gives us these master cells, these stems cells that are essentially the seeds for all of the tissues in our bodies," said George Daley, director of the Stem Cell Transplantation Program at Boston Children's Hospital, who was not involved in the recent studies. "That's why it's so important for medical research."

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Cloning used to make stem cells from adults

Cell lines made by two separate teams could boost the prospects of patient-specific therapies

This colony of embryonic stem cells, created from a type 1 diabetes patient, is one of the first to be cloned from an adult human. Credit:Bjarki Johannesson, NYSCF

Two research groups have independently produced human embryonic stem-cell lines from embryos cloned from adult cells. Their success could reinvigorate efforts to use such cells to make patient-specific replacement tissues for degenerative diseases, for example to replace pancreatic cells in patients with type 1 diabetes. But further studies will be needed before such cells can be tested as therapies.

The first stem-cell lines from cloned human embryos were reported in May last year by a team led by reproductive biology specialist Shoukhrat Mitalipov of the Oregon Health & Science University in Beaverton (see 'Human stem cells created by cloning'). Those cells carried genomes taken from fetal cells or from cells of an eight-month-old baby, and it was unclear whether this would be possible using cells from older individuals. (Errors were found in Mitalipov's paper, but were not deemed to affect the validity of its results.)

Now two teams have independently announced success. On 17 April, researchers led by Young Gie Chung and Dong Ryul Lee at the CHA University in Seoul reported inCell Stem Cellthat they had cloned embryonic stem-cell (ES cell) lines made using nuclei from two healthy men, aged 35 and 75. And in a paper published onNature's website today, a team led by regenerative medicine specialist Dieter Egli at the New York Stem Cell Foundation Research Institute describes ES cells derived from a cloned embryo containing the DNA from a 32-year-old woman with type 1 diabetes. The researchers also succeeded in differentiating these ES cells into insulin-producing cells.

Nuclear transfer To produce the cloned embryos, all three groups used an optimized version of the laboratory technique called somatic-cell nuclear transfer (SCNT), where the nucleus from a patient's cell is placed into an unfertilized human egg which has been stripped of its own nucleus. This reprograms the cell into an embryonic state. SCNT was the technique used to create the first mammal cloned from an adult cell, Dolly the sheep, in 1996.

The studies show that the technique works for adult cells and in multiple labs, marking a major step. It's important for several reasons, says Robin Lovell-Badge, a stem-cell biologist at the MRC National Institute for Medical Research in London.

At present, studies to test potential cell therapies derived from ES cells are more likely to gain regulatory approval than those testing therapies derived from induced pluripotent stem (iPS) cells, which are made by adding genes to adult cells to reprogram them to an embryonic-like state. Compared with iPS cells, ES cells are less variable, says Lovell-Badge. Therapies for spinal-cord injury and eye disease using non-cloned ES cells have already been tested in human trials. But while many ES cell lines have been made using embryos left over from fertility treatments, stem cells made from cloned adult cells are genetically matched to patients and so are at less risk of being rejected when transplanted.

Ethically fraught Lovell-Badge says cloned embryos could also be useful in other ways, in particular to improve techniques for reprogramming adult cells and to study cell types unique to early-stage embryos, such as those that go on to form the placenta.

Few, however, expect a huge influx of researchers making stem cells from cloned human embryos. The technique is expensive, technically difficult and ethically fraught. It creates an embryo only for the purpose of harvesting its cells. Obtaining human eggs also requires regulatory clearance to perform an invasive procedure on healthy young women, who are paid for their time and discomfort.

Read the original here:
Stem Cells Made from Cloned Human Embryos

Bjarki Johannesson, NYSCF

This colony of embryonic stem cells, created from a type 1 diabetes patient, is one of the first to be cloned from an adult human.

Two research groups have independently produced human embryonic stem-cell lines from embryos cloned from adult cells. Their success could reinvigorate efforts to use such cells to make patient-specific replacement tissues for degenerative diseases, for example to replace pancreatic cells in patients with type 1 diabetes. But further studies will be needed before such cells can be tested as therapies.

The first stem-cell lines from cloned human embryos were reported in May last year by a team led by reproductive biology specialist Shoukhrat Mitalipov of the Oregon Health & Science University in Beaverton (see 'Human stem cells created by cloning'). Those cells carried genomes taken from fetal cells or from cells of an eight-month-old baby1, and it was unclear whether this would be possible using cells from older individuals. (Errors were found in Mitalipov's paper, but were not deemed to affect the validity of its results.)

Now two teams have independently announced success. On 17 April, researchers led by Young Gie Chung and Dong Ryul Lee at the CHA University in Seoul reported inCell Stem Cell that they had cloned embryonic stem-cell (ES cell) lines made using nuclei from two healthy men, aged 35 and 752. And in a paper published on Nature's website today, a team led by regenerative medicine specialist Dieter Egli at the New York Stem Cell Foundation Research Institute describes ES cells derived from a cloned embryo containing the DNA from a 32-year-old woman with type 1 diabetes. The researchers also succeeded in differentiating these ES cells into insulin-producing cells3.

To produce the cloned embryos, all three groups used an optimized version of the laboratory technique called somatic-cell nuclear transfer (SCNT), where the nucleus from a patient's cell is placed into an unfertilized human egg which has been stripped of its own nucleus. This reprograms the cell into an embryonic state. SCNT was the technique used to create the first mammal cloned from an adult cell, Dolly the sheep, in 1996.

The studies show that the technique works for adult cells and in multiple labs, marking a major step. It's important for several reasons, says Robin Lovell-Badge, a stem-cell biologist at the MRC National Institute for Medical Research in London.

At present, studies to test potential cell therapies derived from ES cells are more likely to gain regulatory approval than those testing therapies derived from induced pluripotent stem (iPS) cells, which are made by adding genes to adult cells to reprogram them to an embryonic-like state. Compared with iPS cells, ES cells are less variable, says Lovell-Badge. Therapies for spinal-cord injury and eye disease using non-cloned ES cells have already been tested in human trials. But while many ES cell lines have been made using embryos left over from fertility treatments, stem cells made from cloned adult cells are genetically matched to patients and so are at less risk of being rejected when transplanted.

Lovell-Badge says cloned embryos could also be useful in other ways, in particular to improve techniques for reprogramming adult cells and to study cell types unique to early-stage embryos, such as those that go on to form the placenta.

Few, however, expect a huge influx of researchers making stem cells from cloned human embryos. The technique is expensive, technically difficult and ethically fraught. It creates an embryo only for the purpose of harvesting its cells. Obtaining human eggs also requires regulatory clearance to perform an invasive procedure on healthy young women, who are paid for their time and discomfort.

Original post:
Stem cells made by cloning adult humans

Using somatic cell nuclear transfer, a team of scientists led by Dr. Dieter Egli at the New York Stem Cell Foundation (NYSCF) Research Institute and Dr. Mark Sauer at Columbia University Medical Center has created the first disease-specific embryonic stem cell line with two sets of chromosomes.

As reported today in Nature, the scientists derived embryonic stem cells by adding the nuclei of adult skin cells to unfertilized donor oocytes using a process called somatic cell nuclear transfer (SCNT). Embryonic stem cells were created from one adult donor with type 1 diabetes and a healthy control. In 2011, the team reported creating the first embryonic cell line from human skin using nuclear transfer when they made stem cells and insulin-producing beta cells from patients with type 1 diabetes. However, those stem cells were triploid, meaning they had three sets of chromosomes, and therefore could not be used for new therapies.

The investigators overcame the final hurdle in making personalized stem cells that can be used to develop personalized cell therapies. They demonstrated the ability to make a patient-specific embryonic stem cell line that has two sets of chromosomes (a diploid state), the normal number in human cells. Reports from 2013 showed the ability to reprogram fetal fibroblasts using SCNT; however, this latest work demonstrates the first successful derivation by SCNT of diploid pluripotent stem cells from adult and neonatal somatic cells.

"From the start, the goal of this work has been to make patient-specific stem cells from an adult human subject with type 1 diabetes that can give rise to the cells lost in the disease," said Dr. Egli, the NYSCF scientist who led the research and conducted many of the experiments. "By reprograming cells to a pluripotent state and making beta cells, we are now one step closer to being able to treat diabetic patients with their own insulin-producing cells."

"I am thrilled to say we have accomplished our goal of creating patient-specific stem cells from diabetic patients using somatic cell nuclear transfer," said Susan L. Solomon, CEO and co-founder of NYSCF. "I became involved with medical research when my son was diagnosed with type 1 diabetes, and seeing today's results gives me hope that we will one day have a cure for this debilitating disease. The NYSCF laboratory is one of the few places in the world that pursues all types of stem cell research. Even though many people questioned the necessity of continuing our SCNT work, we felt it was critical to advance all types of stem-cell research in pursuit of cures. We don't have a favorite cell type, and we don't yet know what kind of cell is going to be best for putting back into patients to treat their disease."

The research is the culmination of an effort begun in 2006 to make patient-specific embryonic stem cell lines from patients with type 1 diabetes. Ms. Solomon opened NYSCF's privately funded laboratory on March 1, 2006, to facilitate the creation of type 1 diabetes patient-specific embryonic stem cells using SCNT. Initially, the stem cell experiments were done at Harvard and the skin biopsies from type 1 diabetic patients at Columbia; however, isolation of the cell nuclei from these skin biopsies could not be conducted in the federally funded laboratories at Columbia, necessitating a safe-haven laboratory to complete the research. NYSCF initially established its lab, now the largest independent stem cell laboratory in the nation, to serve as the site for this research.

In 2008, all of the research was moved to the NYSCF laboratory when the Harvard scientists determined they could no longer move forward, as restrictions in Massachusetts prevented their obtaining oocytes. Dr. Egli left Harvard University and joined NYSCF; at the same time, NYSCF forged a collaboration with Dr. Sauer who designed a unique egg-donor program that allowed the scientists to obtain oocytes for the research.

"This project is a great example of how enormous strides can be achieved when investigators in basic science and clinical medicine collaborate. I feel fortunate to have been able to participate in this important project," said Dr. Sauer. Dr. Sauer is vice chair of the Department of Obstetrics and Gynecology, professor of obstetrics and gynecology, and chief of reproductive endocrinology at Columbia University Medical Center and program director of assisted reproduction at the Center for Women's Reproductive Care.

Patients with type 1 diabetes lack insulin-producing beta cells, resulting in insulin deficiency and high blood-sugar levels. Therefore, producing beta cells from stem cells for transplantation holds promise as a treatment and potential cure for type 1 diabetes. Because the stem cells are made using a patient's own skin cells, the beta cells for replacement therapy would be autologous, or from the patient, matching the patient's DNA.

Generating autologous beta cells using SCNT is only the first step in developing a complete cell replacement therapy for type 1 diabetes. In type 1 diabetes, the body's immune system attacks its own beta cells; therefore, further work is underway at NYSCF, Columbia, and other institutions to develop strategies to protect existing and therapeutic beta cells from attack by the immune system, as well as to prevent such attack.

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First disease-specific human embryonic stem cell line by nuclear transfer

Regenerative medicine took a step forward on Monday with the announcement of the creation of the first disease-specific line of embryonic stem cells made with a patient's own DNA.

These cells, which used DNA from a 32-year-old woman who had developed Type-1 diabetes at the age of ten, might herald the daystill far in the futurewhen scientists replace dysfunctional cells with healthy cells identical to the patient's own but grown in the lab.

The work was led by Dieter Egli of the New York Stem Cell Foundation (NYSCF) and was published Monday in Nature.

"This is a really important step forward in our quest to develop healthy, patient-specific stem cells that can be used to replace cells that are diseased or dead," said Susan Solomon, chief executive officer of NYSCF, which she co-founded in 2005 partly to search for a cure for her son's diabetes.

Stem cells could one day be used to treat not only diabetes but also other diseases, such as Parkinson's and Alzheimer's.

Embryonic Stem Cells Morph Into Beta Cells

In Type 1 diabetes, the body loses its ability to produce insulin when insulin-producing beta cells in the pancreas become damaged. Ideally this problem could be corrected with replacement therapy, using stem cells to create beta cells the body would recognize as its own because they contain the patient's own genome. This is the holy grail of personalized medicine.

To create a patient-specific line of embryonic stem cells, Egli and his colleagues used a technique known as somatic cell nuclear transfer. They took skin cells from the female patient, removed the nucleus from one cell and then inserted it into a donor egg cellan oocytefrom which the nucleus had been removed.

They stimulated the egg to grow until it became a blastocyst, a hundred-cell embryo in which some cells are "pluripotent," or capable of turning into any type of cell in the body. The researchers then directed a few of those embryonic stem cells to become beta cells. To their delight, the beta cells in the lab produced insulin, just as they would have in the body.

This research builds on work done last year in which scientists from the Oregon Health and Science University used the somatic cell nuclear transfer technique with skin cells from a fetus. It also advances previous work done by Egli and his colleagues in 2011, in which they created embryonic stem cell lines with an extra set of chromosomes. (The new stem cells, and the ones from Oregon, have the normal number of chromosomes.)

Originally posted here:
Scientists Create Personalized Stem Cells, Raising Hopes for Diabetes Cure

Health

After years of failed attempts, researchers have finally generated stem cells from adults using the same cloning technique that produced Dolly the sheep in 1996.

A previous claim that Korean investigators had succeeded in the feat turned out to be fraudulent. Then last year, a group at Oregon Health & Science University generated stem cells using the Dolly technique, but with cells from fetuses and infants.

MORE: Stem-Cell Research: The Quest Resumes

In this case, cells from a 35-year-old man and a 75-year-old man were used to generate two separate lines of stem cells. The process, known as nuclear transfer, involves taking the DNA from a donor and inserting it into an egg that has been stripped of its DNA. The resulting hybrid is stimulated to fuse and start dividing; after a few days the embryo creates a lining of stem cells that are destined to develop into all of the cells and tissues in the human body. Researchers extract these cells and grow them in the lab, where they are treated with the appropriate growth factors and other agents to develop into specific types of cells, like neurons, muscle, or insulin-producing cells.

Reporting in the journal Cell Stem Cell, Dr. Robert Lanza, chief scientific officer at biotechnology company Advanced Cell Technology, and his colleagues found that tweaking the Oregon teams process was the key to success with reprogramming the older cells. Like the earlier team, Lanzas group used caffeine to prevent the fused egg from dividing prematurely. Rather than leaving the egg with its newly introduced DNA for 30 minutes before activating the dividing stage, they let the eggs rest for about two hours. This gave the DNA enough time to acclimate to its new environment and interact with the eggs development factors, which erased each of the donor cells existing history and reprogrammed it to act like a brand new cell in an embryo.

VIDEO: Breakthrough in Cloning Human Stem Cells: Explainer

The team, which included an international group of stem cell scientists, used 77 eggs from four different donors. They tested their new method by waiting for 30 minutes before activating 38 of the resulting embryos, and waiting two hours before triggering 39 of them. None of the 38 developed into the next stage, while two of the embryos getting extended time did. There is a massive molecular change occurring. You are taking a fully differentiated cell, and you need to have the egg do its magic, says Lanza. You need to extend the reprogramming time before you can force the cell to divide.

While a 5% efficiency may not seem laudable, Lanza says that its not so bad given that the stem cells appear to have had their genetic history completely erased and returned to that of a blank slate. This procedure works well, and works with adult cells, says Lanza.

The results also teach stem cell scientists some important lessons. First, that the nuclear transfer method that the Oregon team used is valid, and that with some changes it can be replicated using older adult cells. It looks like the protocols we described are real, they are universal, they work in different hands, in different labs and with different cells, says Shoukhrat Mitalopov, director of the center for embryonic cell and gene therapy at Oregon Health & Science University, and lead investigator of that study.

Originally posted here:
Researchers Clone Cells From Two Adult Men

The first volunteers are expected to be treated by late 2016. If successful, the trial could pave the way to the wide-scale use of artificial blood derived from stem cells.

Blood cells freshly made in the laboratory are likely to have a longer life span than those taken from donors, which typically last no more than 120 days.

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They would also be free from infectious agents such as viruses or the rogue prion proteins that cause Creuzfeldt-Jakob Disease (CJD). Professor Marc Turner, medical director at the Scottish National Blood Transfusion Service (SNBTS), who is leading the 5 million project at the University of Edinburgh, said: "Producing a cellular therapy which is of the scale, quality and safety required for human clinical trials is a very significant challenge. But if we can achieve success with this first-in-man clinical study it will be an important step forward to enable populations all over the world to benefit from blood transfusions.

"These developments will also provide information of value to other researchers working on the development of cellular therapies."

The pilot study will involve no more than about three patients, who may be healthy volunteers or individuals suffering from a red blood cell disorder such as thalassaemia. They will receive a small, five millilitre dose of laboratory-made blood to see how it behaves and survives in their bodies.

The blood cells will be created from ordinary donated skin cells called fibroblasts which are genetically reprogrammed into a stem cell-like state.

The resulting induced pluripotent stem (iPS) cells have the same ability as embryonic stem cells to develop into virtually any kind of body tissue.

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Scientists pioneer lab-grown red cells

The first volunteers are expected to be treated by late 2016. If successful, the trial could pave the way to the wide-scale use of artificial blood derived from stem cells.

Blood cells freshly made in the laboratory are likely to have a longer life span than those taken from donors, which typically last no more than 120 days.

Loading article content

They would also be free from infectious agents such as viruses or the rogue prion proteins that cause Creuzfeldt-Jakob Disease (CJD).

Professor Marc Turner, medical director at the Scottish National Blood Transfusion Service (SNBTS), who is leading the 5 million project at the University of Edinburgh, said: "Producing a cellular therapy which is of the scale, quality and safety required for human clinical trials is a very significant challenge.

"But if we can achieve success with this first-in-man clinical study it will be an important step forward to enable populations all over the world to benefit from blood transfusions.

"These developments will also provide information of value to other researchers working on the development of cellular therapies."

The pilot study will involve no more than about three patients, who may be healthy volunteers or individuals suffering from a red blood cell disorder such as thalassaemia.

They will receive a small, five millilitre dose of laboratory-made blood to see how it behaves and survives in their bodies.

The blood cells will be created from ordinary donated skin cells called fibroblasts which are genetically reprogrammed into a stem cell-like state.

Read the original here:
In the blood: Scottish scientists pioneer lab-grown cells

14/04/2014 - 13:40:33Back to World Home

Red blood cells grown in a laboratory are to be tested in patients for the first time by pioneering scientists.

The first volunteers are expected to be treated by late 2016. If successful, the trial could pave the way to the wide-scale use of artificial blood derived from stem cells.

Blood cells freshly made in the laboratory are likely to have a longer life span than those taken from donors, which typically last no more than 120 days.

They would also be free from infectious agents such as viruses or the rogue prion proteins that cause Creuzfeldt-Jakob Disease (CJD).

Professor Marc Turner, medical director at the Scottish National Blood Transfusion Service (SNBTS), who is leading the 5m project at the University of Edinburgh, said: Producing a cellular therapy which is of the scale, quality and safety required for human clinical trials is a very significant challenge. But if we can achieve success with this first-in-man clinical study it will be an important step forward to enable populations all over the world to benefit from blood transfusions.

These developments will also provide information of value to other researchers working on the development of cellular therapies.

The pilot study will involve no more than about three patients, who may be healthy volunteers or individuals suffering from a red blood cell disorder such as thalassaemia.

They will receive a small, five millilitre dose of laboratory-made blood to see how it behaves and survives in their bodies.

The blood cells will be created from ordinary donated skin cells called fibroblasts which are genetically reprogrammed into a stem cell-like state.

View original post here:
Scientists to test artificial blood in humans

Bradley J. Fikes

Stem-cell biologist Mahendra Rao expected five projects to receive support to set up clinical trials.

Stem-cell researchers at the US National Institutes of Health (NIH) have been left frustrated and confused following the demise of the agencys Center for Regenerative Medicine (CRM). The intramural programmes director, stem-cell biologist Mahendra Rao, left the NIH, in Bethesda, Maryland, on 28March, and the centres website was taken down on 4 April. Although no official announcement had been made at the time Nature went to press, NIH officials say that they are rethinking how they will conduct in-house stem-cell research.

Researchers affiliated with the centre say that they have been left in the dark. When contacted by Nature on 7April, George Daley, a stem-cell biologist at Harvard Medical School in Boston, Massachusetts, and a member of the centres external advisory board, said that he had not yet been told of Raos departure or the centres closure.

The CRM was established in 2010 to centralize the NIHs stem-cell programme. Its goal was to develop useful therapies from induced pluripotent stem (iPS) cells adult cells that have been converted into embryonic-like stem cells and shepherd them towards clinical trials and regulatory approval. Its budget was intended to be $52million over seven years.

Rao took the helm in 2011. Relations seem to have soured last month owing to an NIH decision to award funding to only one project aiming to move iPS cells into a clinical trial. Rao says he resigned after this became clear. He says that he had hoped that five trials would be funded, especially because the centre had already sorted out complex issues relating to tissue sources, patents and informed consent.

James Anderson, director of the NIHs Division of Program Coordination, Planning, and Strategic Initiatives, which administered the CRM, counters that only one application that made by Kapil Bharti of the National Eye Institute in Bethesda and his colleagues received a high enough score from an external review board to justify continued funding. The team aims to use iPS cells to treat age-related macular degeneration of the retina, and hopes to commence human trials within a few years. Several other proposals, which involved the treatment of cardiac disease, cancer and Parkinsons disease, will not receive funding to ready them for clinical trials. Anderson stresses that Bhartis trial will not be affected by the CRMs closure.

NIH

Therapies based on induced pluripotent stem cells, here differentiating into retinal cells on a scaffold, were the focus of the Center for Regenerative Medicine.

Other human iPS-cell trials are further along. For example, one on macular degeneration designed by Masayo Takahashi at the RIKEN Center for Developmental Biology in Kobe, Japan, began recruiting patients last August.

Link:
NIH stem-cell programme closes

Mouse cells exposed to an acidic environment turned into embryonic-like "STAP" cells. These were used to generate an entire fetus.

A coauthor of a disputed study on a new way generating stem cells through exposure to acid and other stresses has asked for its retraction, it was reported Monday.

Teruhiko Wakayama asked for retraction of two papers describing so-called STAP cells, according to the Yomiuri Shimbun. The papers had been published in the Jan. 30 edition of the journal Nature. Other news outlets, including the Wall Street Journal and the Boston Globe, quickly followed up with the call for retraction.

The original announcement gained worldwide attention because it promised an easy way to generate pluripotent stem cells, which act like embryonic stem cells. Simply immersing cells in an acid bath or squeezing them was enough to reprogram them to the embryonic-like state, the scientists reported. The acronym STAP stands for stimulus-triggered acquisition of pluripotency.

However, researchers attempting to replicate the experiment, including those at the Salk Institute and The Scripps Research Institute in La Jolla, have so far reported failure. And errors in the papers, including duplication of images, have caused scientists to question the findings.

The first author of both papers is Haruko Obokata, 30, of the Riken Center for Developmental Biology in Japan. She was hailed as a scientific prodigy after the research was published. Another coauthor, Charles Vacanti, chairman of the Anesthesiology department at Brigham and Womens Hospital in Boston, had previously said the errors were caused by overwork and didn't affect the results.

As recently as Feb. 27, Wakayama said scientists should give replication efforts a year before passing judgment.

But on Monday, Wakayama said the irregularities render the findings questionable.

"Wakayama said images that show pluripotency of STAP cells look almost identical to those used in Obokatas doctoral thesis about pluripotent stem cells that exist in human body," the Yomiuri Shimbun reported.

Wakayama is probably acting out of a sense of duty, said Jeanne Loring, a stem cell scientist at The Scripps Research Institute.

Visit link:
STAP cells paper coauthor asks for retraction

PUBLIC RELEASE DATE:

9-Mar-2014

Contact: Henry Rummins h.rummins@ucl.ac.uk 44-207-679-9063 University College London

Japanese pharmaceutical company Takeda will work with University College London (UCL) to drive research into tackling muscle disorders, in particular muscular dystrophy.

The research which is being conducted by the research group of Dr Francesco Saverio Tedesco is being supported through funding of $250,000 from the company's New Frontier Sciences group. Takeda's NFS aims to support innovative, cutting-edge research which could eventually lead to drug discovery and development.

Dr Tedesco's team will focus on the study of muscular regeneration and the potential for stem cell therapies to treat muscular dystrophy, in particular induced pluripotent (iPS) stem cells.

The team is also investigating the potential for treating muscular dystrophy through developing novel gene and cell therapy strategies using artificial human chromosomes and novel biomaterials.

Using this approach, Dr Tedesco hopes to overcome a number of current limitations to developing effective treatments for muscular dystrophies. It is hoped that through the use of these modified stem cells, large quantities of progenitor cells could be produced to be transplanted into a patient's muscle following genetic correction or to be used for drug development platforms.

Importantly, the team will attempt to produce these cells which can be applied more easily in a clinical context, in order to reduce the hurdles that might limit their possible future use in clinical studies.

Through previous work using a mouse model of Duchenne muscular dystrophy, the team has already demonstrated the potential of pre-clinical gene replacement therapy using an artificial human chromosome.

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Takeda and UCL to work together to tackle muscle disorders

Doubts keep growing about the stunning discovery that super stem cells could be created merely by placing white blood cells from young mice in acid or otherwise stressing them, says Paul Knoepfler, a stem cell researcher at UC Davis.

Among other inconsistencies, Knoepfler referred to several unexplained anomalies in images of these STAP cells in two papers, published by the prestigious journal Nature on Jan. 29. One image appears to suggest signs that virtually all cells treated with an acid bath were being reprogrammed, a result that would be extraordinary. Stem cell reprogramming to date has been inefficient, with a low percentage of treated cells being reprogrammed.

"The more I look at these two STAP papers, the more concerned I get ... The bottom line for me now is that some level a part of me still clings to a tiny and receding hope this has all been overblown due to simple misunderstandings, but that seems increasingly unlikely," Knoepfler wrote Sunday on his blog, IPS Cell.

This undated image made available by the journal Nature shows a mouse embryo formed with specially-treated cells from a newborn mouse that had been transformed into stem cells. Researchers in Boston and Japan say they created stem cells from various tissues of newborn mice. If the same technique works for humans, it may provide a new way to grow tissue for treating illnesses like diabetes and Parkinson's disease. The report was published online on Wednesday, Jan. 29, 2014 in the journal Nature. (AP Photo/RIKEN Center for Developmental Biology, Haruko Obokata)

Nature is conducting its own investigation, Knoepfler noted. But in addition, the journal should release "unmodified, original versions" of the images and data in the papers, Knoepfler wrote.

The images contained "minor errors" that didn't change the basic findings, said Charles Vacanti, a Harvard University professor who is part of the scientific team reporting the discovery, according to a Feb. 22 article in a Japanese newspaper, the Asahi Shimbun.

Controversy is normal for any major scientific advance. Skeptics must be converted, and the only way to do that is to show the data. The 1997 announcement of the first mammalian clone, Dolly the sheep, was greeted with considerable doubt because it was believed that genetic imprinting made such cloning impossible. But others were eventually able to confirm the finding.

In this case, doubters say such an apparently easy method of reprogramming cells would generate pluripotent stem cells far too easily, because stress is common in animals. Such stem cells are known to cause tumors, so evolution should have selected against such a response.

Nature's own role has been criticized. The journal was taken to task for its handling of online journalism Feb. 20 by another stem cell blogger, Alexey Bersenev. He chided Nature for not linking to sources.

"In scientific journalism, every claim must be linked to appropriate original source," Berseney wrote. "Nature consistently refuses to acknowledge bloggers, online discussions and other web resources with valid credible information. This is not acceptable for sci journalism."

The rest is here:
STAP stem cell doubts keep proliferating

La Jolla, CAA study led by researchers at the Salk Institute for Biological Studies, has catapulted the field of regenerative medicine significantly forward, proving in principle that a human genetic disease can be cured using a combination of gene therapy and induced pluripotent stem (iPS) cell technology. The study, published in the May 31, 2009 early online edition of Nature, is a major milestone on the path from the laboratory to the clinic.

"It's been ten years since human stem cells were first cultured in a Petri dish," says the study's leader Juan-Carlos Izpisa Belmonte, Ph.D., a professor in the Gene Expression Laboratory and director of the Center of Regenerative Medicine in Barcelona (CMRB), Spain. "The hope in the field has always been that we'll be able to correct a disease genetically and then make iPS cells that differentiate into the type of tissue where the disease is manifested and bring it to clinic."

Genetically-corrected fibroblasts from Fanconi anemia patients (shown in green at the top) are reprogrammed to generate induced pluripotent stem cells, which, in turn, can be differentiated into disease-free hematopoietic progenitors, capable of producing blood cells in vitro (bottom: Erythroid colonies.)

Image: Courtesy of Dr. Juan-Carlos Belmonte, Salk Institute for Biological Studies.

Although several studies have demonstrated the efficacy of the approach in mice, its feasibility in humans had not been established. The Salk study offers the first proof that this technology can work in human cells.

Belmonte's team, working with Salk colleague Inder Verma, Ph.D., a professor in the Laboratory of Genetics, and colleagues at the CMRB, and the CIEMAT in Madrid, Spain, decided to focus on Fanconi anemia (FA), a genetic disorder responsible for a series of hematological abnormalities that impair the body's ability to fight infection, deliver oxygen, and clot blood. Caused by mutations in one of 13 Fanconi anemia (FA) genes, the disease often leads to bone marrow failure, leukemia, and other cancers. Even after receiving bone marrow transplants to correct the hematological problems, patients remain at high risk of developing cancer and other serious health conditions.

After taking hair or skin cells from patients with Fanconi anemia, the investigators corrected the defective gene in the patients' cells using gene therapy techniques pioneered in Verma's laboratory. They then successfully reprogrammed the repaired cells into induced pluripotent stem (iPS) cells using a combination of transcription factors, OCT4, SOX2, KLF4 and cMYC. The resulting FA-iPS cells were indistinguishable from human embryonic stem cells and iPS cells generated from healthy donors.

Since bone marrow failure as a result of the progressive decline in the numbers of functional hematopoietic stem cells is the most prominent feature of Fanconi anemia, the researchers then tested whether patient-specific iPS cells could be used as a source for transplantable hematopoietic stem cells. They found that FA-iPS cells readily differentiated into hematopoietic progenitor cells primed to differentiate into healthy blood cells.

"We haven't cured a human being, but we have cured a cell," Belmonte explains. "In theory we could transplant it into a human and cure the disease."

Although hurdles still loom before that theory can become practice-in particular, preventing the reprogrammed cells from inducing tumors-in coming months Belmonte and Verma will be exploring ways to overcome that and other obstacles. In April 2009, they received a $6.6 million from the California Institute Regenerative Medicine (CIRM) to pursue research aimed at translating basic science into clinical cures.

Link:
Genetic Re-disposition: Combined stem cell-gene therapy ...