Mice have been poked, prodded, injected and dissected in the name of science. But there are limits to what mice can teach us especially when it comes to stem cell therapies. For the first time, researchers haveturned skin cells into bone in a creature more closely related to humans: monkeys.

In a study published Thursday in the journal Cell Reports, scientists report that they regrew bone in 25rhesus macaques using induced pluripotent stem cells (iPSCs) taken from the creatures skin. Since macaques are more closely related to humans, their discovery could help push stem cell therapies into early clinical trials in humans.

While this is the good news, the bad news is that iPSCs can also seed tumors in monkeys; however, the tumors grew at a far slower rate than in previous studies in mice. This finding further emphasizes the key role primates likely will play in testing the safety of potential stem cell therapies.

Repairing Bone

Researchers used a common procedure to reprogram macaque skin cells, and coaxed them into pluripotent cells that were capable of building bone. They seeded these cells into ceramic scaffolds, which are already used by surgeons used to reconstruct bone. The cells took, and the monkeys successfully grew new bone.

In some experiments, the monkeys formed teratomas nasty tumors that can contain teeth and hair when they were injected with undifferentiated iPSCs, or cells that have the potential to change into any kind of cell. However, the tumors grew 20 times slower than in mice, highlighting an important difference between mice and monkeys.

Fortunately, tumors did not form in monkeys that were injected with differentiated iPSCs, or cells that were programmed to createbone cells.

Advancing Research

Researchers say their successful procedure proves that monkeys willplay an important rolein research on therapies using iPSCs. These monkeys will help scientists test and analyze risks associated with the therapies and improve their safety.

More here:
Successful Stem Cell Therapy in Monkeys is First of Its Kind

Dr. Broyles #39; Cartilage Regeneration: Why Bone Marrow Stem Cells?
Dr. Broyles highlights the differences between Dr. Saw #39;s methods and his own, including FDA regulations in the US regarding autologous stem cells. For more i...

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Dr. Broyles' Cartilage Regeneration: Why Bone Marrow Stem Cells? - Video

THURSDAY, May 15, 2014 (HealthDay News) -- Although the very concept of cancer stem cells has been controversial, new research provides proof that these distinct types of cells exist in humans.

Using genetic tracking, researchers found that a gene mutation tied to cancer's development can be traced back to cancer stem cells. These cells are at the root of cancer and responsible for supporting the growth and progression of the disease, the scientists report.

Cancer stem cells are able to replenish themselves and produce other types of cancer cells, just as healthy cells produce other normal cells, the study's British and European authors explained.

"It's like having dandelions in your lawn. You can pull out as many as you want, but if you don't get the roots they'll come back," study first author Dr. Petter Woll, of the MRC Weatherall Institute for Molecular Medicine at the University of Oxford, said in a university news release.

The researchers, led by a team of scientists at Oxford and the Karolinska Institute in Sweden, said their findings could have significant implications for cancer treatment. They explained that by targeting cancer stem cells, doctors could not only get rid of a patient's cancer but also prevent any remaining cancer cells from sustaining the disease.

The study, published May 15 in Cancer Cell, involved 15 patients diagnosed with myelodysplastic syndromes (MDS), a type of cancer that often develops into acute myeloid leukemia, a form of blood cancer.

The researchers examined the cancer cells in the patients' bone marrow. Four of the patients were also monitored over time. One patient was followed for two years. Two patients were followed for 30 months and another patient was monitored for 10 years.

According to the researchers, in prior studies citing the existence of cancer stem cells, the lab tests that were used to identify these cells were considered by many to be unreliable.

However, "In our studies we avoided the problem of unreliable lab tests by tracking the origin and development of cancer-driving mutations in MDS patients," explained study leader Sten Eirik Jacobsen, of Oxford's MRC Molecular Haematology Unit and the Weatherall Institute for Molecular Medicine.

According to the research, a distinct group of MDS cells had all the characteristics of cancer stem cells, and only these particular cancer cells appeared able to cause tumor spread.

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Scientists get closer to the stem cells that may drive cancers

Concerns that stem cells could cause cancer in recipients are fading further with a new study

New bone formation (stained bright green under ultra-violet light) was seen in monkeys given their own reprogrammed stem cells. Courtesy of Nature magazine

A major concern over using stem cells is the risk of tumors: but now a new study shows that It takes a lot of effort to get induced pluripotent stem (iPS) cells to grow into tumors after they have been transplanted into a monkey. The findings will bolster the prospects of one day using such cells clinically in humans.

Making iPS cells from an animal's own skin cells and then transplanting them back into the creature also does not trigger an inflammatory response as long as the cells have first been coaxed to differentiate towards a more specialized cell type. Both observations, published inCell Reports today, bode well for potential cell therapies.

It's important because the field is very controversial right now, saysAshleigh Boyd,a stem-cell researcher at University College London, who was not involved in the work. It is showing that the weight of evidence is pointing towards the fact that the cells won't be rejected.

Pluripotent stem cells can be differentiated into many different specialized cell types in culture and so are touted for their potential as therapies to replace tissue lost in diseases such as Parkinsons and some forms of diabetes and blindness. iPS cells, which are made by reprogramming adult cells, have an extra advantage because transplants made from them could be genetically matched to the recipient.

Researchers all over the world are pursuing therapies based on iPS cells, and a group in Japan began enrolling patients for a human study last year. But work in mice has suggested controversially that even genetically matched iPS cellscan trigger an immune response, and pluripotent stem cells can also form slow-growing tumors, another safety concern.

Closer to human Cynthia Dunbar, a stem-cell biologist at the National Institutes of Health in Bethesda, Maryland, who led the new study, decided to evaluate both concerns in healthy rhesus macaques. Human stem cells are normally only studied for their ability to form tumors in mice as a test of pluripotency if the animals immune systems are compromised, she says.

We really wanted to set up a model that was closer to human. It was somewhat reassuring that in a normal monkey with a normal immune system you had to give a whole lot of immature cells to get any kind of tumour to grow, and they were very slow growing.

Dunbar and her team made iPS cells from skin and white blood cells from two rhesus macaques, and transplanted the iPS cells back into the monkeys that provided them. It took 20 times as many iPS cells to form a tumor in a monkey, compared with the numbers needed in an immunocompromised mouse. Such information will be valuable for assessing safety risks of potential therapies, Dunbar says. And although the iPS cells did trigger a mild immune response attracting white blood cells and causing local inflammation iPS cells that had first been differentiated to a more mature state did not.

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New Stem Cell Finding Bodes Well for Future Medical Use in Humans

A number of ingredients like ceramides, collagen, stem cells and antioxidants that are commonly associated with cosmetics are being featured in products for the hair. Do they work as well?

In the quest for a healthy and shining mane, a number of new products are being launched in the market on a regular basis. It has been observed that many of these are said to contain elements that are normally associated with skin care. Products with collagen, ceramides, hyaluronic acid, stem cells and so on have long been proven beneficial to plump up skin, reduce fine lines, lighten dark spots and keep skin healthy and radiant. However, recently a number of these have been seen in hair care products like shampoos and conditioners. The question remains though is of they work just as well on the mane. Copper peptides, for example is considered an effective skin regeneration ingredient and research shows it works well for the scalp too producing thicker, healthier hair. Ceramides can be effective in forming a protective coat around the hair shaft and strengthening it, while collagen helps hair hold onto moisture making it look thicker and fuller. Antioxidants are said to neutralise the free radicals preventing dullness of locks.

SCALP IS SIMILAR TO SKIN Tisha Kapur Khurana, beauty expert and executive director, Bottega di Lungavita explains similar ingredients can be used on the skin and hair sometimes because the scalp is covered with thicker skin similar to the rest of our body. It is a thick layer of skin with many sebaceous glands which produce oil or sebum to protect the hair. Collagen is a protein that is found in the body and is a necessity for good health. The collagen supplements let hair grow long and strong. It increases the body's natural hair-building proteins. Moreover, if applied to the scalp, it can reduce the look and dryness of grey hair. Even stem cells work as the hair follicles contain cells which may lead to successfully treating baldness. When buying a product you should always consider the hair type curly or straight as well as thick or fine and accordingly choose products, she says.

BE CAREFUL It is advisable not to use similar products for your hair and skin. Your skin is very tender and it needs really mild products to cleanse and clear the dirt and impurities. On the other hand, while you do need mild products for your hair as well, the shampoos and conditioners are mild but effective enough to cleanse the grime, dandruff and other impurities that get lodged in your scalp, explains Priti Mehta, founder and director, Omved. She adds, Standard cosmetics often include synthetic and sometimes even animal-derived ingredients. When you use natural options for your skin and hair, it is likely to help your skin feel and breathe better. Anything that has SLS, parabens, preservatives, fragrance, and colours to name a few listed on it should be avoided.

HAVE SOME BENEFITS Dr Apratim Goel, dermatologist, Cutis Skin Studio says some of these ingredients can work. Collagen or ceramides are larger molecules which are doubtful on skin as well. However these ingredients have been used regularly in hair care products. However, there is no controlled studies of efficacy of these ingredients in hair. Stem cells and antioxidants, though, do work for hair. Stem cell injections are a regular treatment for boosting hair growth. Further, plant stem cells are available as hair serums and give good results against hair loss. Regarding antioxidants, they are very important for hair care as hair especially coloured or treated locks are very prone to damage from sun as well as chemical exposure.

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Do products used in cosmetics work for the hair?

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 ...

In this image, the top row shows the stem cells transplanted into the mouse spinal cord. The lower row shows a close-up of the stem cells (brown). By day 7 post-transplant, the stem cells are no longer detectable. Within this short period of time, the stem cells have sent chemical signals to the mouses own cells, enabling them to repair the nerve damage caused by MS. (image: Lu Chen)

For patients with multiple sclerosis (MS), current treatment options only address early-stage symptoms of the debilitating disease. Now, new research has found a potential treatment that could both stop disease progression and repair existing damage.

In a study published in Stem Cell Reports, researchers utilized a group of paralyzed mice genetically engineered to have an MS-like condition. Initially, the researchers set out to study the mechanisms of stem cell rejection in the mice. However, two weeks after injecting the mice with human neural stem cells, the researchers made the unexpected discovery that the mice had regained their ability to walk.

This had a lot of luck to do with it; right place, right time co-senior author Jeanne Loring, director of the Center for Regenerative Medicine at The Scripps Research Institute in La Jolla, California, told FoxNews.com. [co-senior author Tom Lane] called me up and said, Youre not going to believe this. He sent me a video, and it showed the mice running around the cages. I said, Are you sure these are the same mice?

Loring, whose lab specializes in turning human stem cells into neural precursor cells, or pluripotent cells, collaborated with Tom Lane, a professor of pathology at the University of Utah whose focus is on neuroinflammatory diseases of the central nervous system. The team was interested in stem cell rejection in MS models in order to understand the underlying molecular and cellular mechanisms contributing to rejection of potential stem cell therapies for the disease.

Multiple sclerosis is an autoimmune disease that affects more than 2.3 million people worldwide. For people with MS, the immune system misguidedly attacks the bodys myelin, the insulating coating on nerve fibers.

In a nutshell, its the rubber sheath that protects the electrical wire; the axon that extends from the nerves cell body is insulated by myelin, Lane, who began the study while at the University of California, Irvine, told FoxNews.com

Once the myelin has been lost, nerve fibers are unable to transmit electric signals efficiently, leading to symptoms such as vision and motor skill problems, fatigue, slurred speech, memory difficulties and depression.

The researchers inadvertent treatment appeared to work in two ways. First, there was a decrease of inflammation within the central nervous system of the mice, preventing the disease from progressing. Secondly, the injected cells released proteins that signaled cells to regenerate myelin and repair existing damage.

While the stem cells were rejected in the mice after 10 days, researchers were able to see improvements for up to six months after initial implantation.

See the original post here:
Stem cell therapy shows promise for multiple sclerosis

Mice have been poked, prodded, injected and dissected in the name of science. But there are limits to what mice can teach us especially when it comes to stem cell therapies. For the first time, researchers haveturned skin cells into bone in a creature more closely related to humans: monkeys.

In a study published Thursday in the journal Cell Reports, scientists report that they regrew bone in 25rhesus macaques using induced pluripotent stem cells (iPSCs) taken from the creatures skin. Since macaques are more closely related to humans, their discovery could help push stem cell therapies into early clinical trials in humans.

While this is the good news, the bad news is that iPSCs can also seed tumors in monkeys; however, the tumors grew at a far slower rate than in previous studies in mice. This finding further emphasizes the key role primates likely will play in testing the safety of potential stem cell therapies.

Repairing Bone

Researchers used a common procedure to reprogram macaque skin cells, and coaxed them into pluripotent cells that were capable of building bone. They seeded these cells into ceramic scaffolds, which are already used by surgeons used to reconstruct bone. The cells took, and the monkeys successfully grew new bone.

In some experiments, the monkeys formed teratomas nasty tumors that can contain teeth and hair when they were injected with undifferentiated iPSCs, or cells that have the potential to change into any kind of cell. However, the tumors grew 20 times slower than in mice, highlighting an important difference between mice and monkeys.

Fortunately, tumors did not form in monkeys that were injected with differentiated iPSCs, or cells that were programmed to createbone cells.

Advancing Research

Researchers say their successful procedure proves that monkeys willplay an important rolein research on therapies using iPSCs. These monkeys will help scientists test and analyze risks associated with the therapies and improve their safety.

Read more here:
Succssful Stem Cell Therapy in Monkeys is First of Its Kind

Researchers have shown for the first time in an animal that is more closely related to humans that it is possible to make new bone from stem-cell-like induced pluripotent stem cells (iPSCs) made from an individual animal's own skin cells. The study in monkeys reported in the Cell Press journal Cell Reports on May 15th also shows that there is some risk that those iPSCs could seed tumors, but that unfortunate outcome appears to be less likely than studies in immune-compromised mice would suggest.

"We have been able to design an animal model for testing of pluripotent stem cell therapies using the rhesus macaque, a small monkey that is readily available and has been validated as being closely related physiologically to humans," said Cynthia Dunbar of the National Heart, Lung, and Blood Institute. "We have used this model to demonstrate that tumor formation of a type called a 'teratoma' from undifferentiated autologous iPSCs does occur; however, tumor formation is very slow and requires large numbers of iPSCs given under very hospitable conditions. We have also shown that new bone can be produced from autologous iPSCs, as a model for their possible clinical application."

Autologous refers to the fact that the iPSCs capable of producing any tissue typein this case bonewere derived from the very individual that later received them. That means that use of these cells in tissue repair would not require long-term or possibly toxic immune suppression drugs to prevent rejection.

The researchers first used a standard recipe to reprogram skin cells taken from rhesus macaques. They then coaxed those cells to form first pluripotent stem cells and then cells that have the potential to act more specifically as bone progenitors. Those progenitor cells were then seeded onto ceramic scaffolds that are already in use by reconstructive surgeons attempting to fill in or rebuild bone. And, it worked; the monkeys grew new bone.

Importantly, the researchers report that no teratoma structures developed in monkeys that had received the bone "stem cells." In other experiments, undifferentiated iPSCs did form teratomas in a dose-dependent manner.

The researchers say that therapies based on this approach could be particularly beneficial for people with large congenital bone defects or other traumatic injuries. Although bone replacement is an unlikely "first in human" use for stem cell therapies given that the condition it treats is not life threatening, the findings in a primate are an essential step on the path toward regenerative clinical medicine.

"A large animal preclinical model for the development of pluripotent or other high-risk/high-reward generative cell therapies is absolutely required to address issues of tissue integration or homing, risk of tumor formation, and immunogenicity," Dunbar said. "The testing of human-derived cells in vitro or in profoundly immunodeficient mice simply cannot model these crucial preclinical safety and efficiency issues."

The NIH team is now working with collaborators on differentiation of the macaque iPSCs into liver, heart, and white blood cells for eventual clinical trials in hepatitis C, heart failure, and chronic granulomatous disease, respectively.

Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.

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First test of pluripotent stem cell therapy in monkeys is successful

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15-May-2014

Contact: University of Oxford news.office@admin.ox.ac.uk 44-186-528-0530 University of Oxford

The gene mutations driving cancer have been tracked for the first time in patients back to a distinct set of cells at the root of cancer cancer stem cells.

The international research team, led by scientists at the University of Oxford and the Karolinska Institutet in Sweden, studied a group of patients with myelodysplastic syndromes a malignant blood condition which frequently develops into acute myeloid leukaemia.

The researchers say their findings, reported in the journal Cancer Cell, offer conclusive evidence for the existence of cancer stem cells.

The concept of cancer stem cells has been a compelling but controversial idea for many years. It suggests that at the root of any cancer there is a small subset of cancer cells that are solely responsible for driving the growth and evolution of a patient's cancer. These cancer stem cells replenish themselves and produce the other types of cancer cells, as normal stem cells produce other normal tissues.

The concept is important, because it suggests that only by developing treatments that get rid of the cancer stem cells will you be able to eradicate the cancer. Likewise, if you could selectively eliminate these cancer stem cells, the other remaining cancer cells would not be able to sustain the cancer.

'It's like having dandelions in your lawn. You can pull out as many as you want, but if you don't get the roots they'll come back,' explains first author Dr Petter Woll of the MRC Weatherall Institute for Molecular Medicine at the University of Oxford.

The researchers, led by Professor Sten Eirik W Jacobsen at the MRC Molecular Haematology Unit and the Weatherall Institute for Molecular Medicine at the University of Oxford, investigated malignant cells in the bone marrow of patients with myelodysplastic syndrome (MDS) and followed them over time.

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Genetic tracking identifies cancer stem cells in human patients

The Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB) in Stuttgart, Germany, has developed a technique to analyze living cells quickly and accurately based on Raman spectroscopy. The non-invasive optical procedure, which can identify the molecular fingerprint of different materials, has primarily been employed in quality control for medications and pharmaceutical substances.

Now biomedical researchers can also use this technology thanks to the research at IGB involving joint projects with universities, industrial partners, and the State of Baden-Wrttemberg. The tmethod is suited to investigating living cells without requiring invasive techniques or altering them with dyes.

In order to characterize stem cells or identify changes to tissues that are caused by tumors, inflammations, fungi, or bacteria, for example, it is now sufficient to determine the individual cells Raman spectrum which is a specialized energy spectrum having particular analytical capability.

Prof. Katja Schenke-Layland from IGB commented, We have developed comprehensive know-how in this area and have advanced the technology from use in pure research to industrial implementation. We can now investigate not just individual cells, but entire tissue structures and organs. Next we want to further refine the technology and develop more applications.

Cell biologists at IGB use a specially developed Raman spectroscope jointly designed and built with physicists at the Fraunhofer Institute for Physical Measurement Techniques (IPM) in Freiburg. The device is compact and can be conveniently used to investigate a wide range of scientific problems. The scientists are accumulating the spectra they have recorded into a database.

Cancer testing

Schenke-Layland added, Each cell has a unique, unmistakable Raman spectrum. Doctors can compare the sample from their patients cells with our database and complete their diagnoses more quickly. The technology is already being employed on a practical basis by industrial partners. The scientists are working at present on a rapid test for cancer diagnosis.

Doctors using mobile Raman spectroscopes during an operation could unambiguously say whether a patient has cancer or not simply by comparing the cell sample with the data base.

Conventional cancer diagnoses are still complicated and prolonged. After excising the tissue for biopsy, it first must be prepared for further analysis for example by suitably sectioning or dying it to identify biomarkers. But this always requires intervention in the specimen and manipulating it in some way, she said.

Diverse applications

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Raman method analyzes live cells quickly and accurately

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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

PUBLIC RELEASE DATE:

15-May-2014

Contact: Mary Beth O'Leary moleary@cell.com 617-397-2802 Cell Press

Researchers have shown for the first time in an animal that is more closely related to humans that it is possible to make new bone from stem-cell-like induced pluripotent stem cells (iPSCs) made from an individual animal's own skin cells. The study in monkeys reported in the Cell Press journal Cell Reports on May 15th also shows that there is some risk that those iPSCs could seed tumors, but that unfortunate outcome appears to be less likely than studies in immune-compromised mice would suggest.

"We have been able to design an animal model for testing of pluripotent stem cell therapies using the rhesus macaque, a small monkey that is readily available and has been validated as being closely related physiologically to humans," said Cynthia Dunbar of the National Heart, Lung, and Blood Institute. "We have used this model to demonstrate that tumor formation of a type called a 'teratoma' from undifferentiated autologous iPSCs does occur; however, tumor formation is very slow and requires large numbers of iPSCs given under very hospitable conditions. We have also shown that new bone can be produced from autologous iPSCs, as a model for their possible clinical application."

Autologous refers to the fact that the iPSCs capable of producing any tissue typein this case bonewere derived from the very individual that later received them. That means that use of these cells in tissue repair would not require long-term or possibly toxic immune suppression drugs to prevent rejection.

The researchers first used a standard recipe to reprogram skin cells taken from rhesus macaques. They then coaxed those cells to form first pluripotent stem cells and then cells that have the potential to act more specifically as bone progenitors. Those progenitor cells were then seeded onto ceramic scaffolds that are already in use by reconstructive surgeons attempting to fill in or rebuild bone. And, it worked; the monkeys grew new bone.

Importantly, the researchers report that no teratoma structures developed in monkeys that had received the bone "stem cells." In other experiments, undifferentiated iPSCs did form teratomas in a dose-dependent manner.

The researchers say that therapies based on this approach could be particularly beneficial for people with large congenital bone defects or other traumatic injuries. Although bone replacement is an unlikely "first in human" use for stem cell therapies given that the condition it treats is not life threatening, the findings in a primate are an essential step on the path toward regenerative clinical medicine.

"A large animal preclinical model for the development of pluripotent or other high-risk/high-reward generative cell therapies is absolutely required to address issues of tissue integration or homing, risk of tumor formation, and immunogenicity," Dunbar said. "The testing of human-derived cells in vitro or in profoundly immunodeficient mice simply cannot model these crucial preclinical safety and efficiency issues."

Read the rest here:
First test of pluripotent stem cell therapy in monkeys is a success

PUBLIC RELEASE DATE:

15-May-2014

Contact: Mika Ono mikaono@scripps.ed 858-784-2052 Scripps Research Institute

LA JOLLA, CAMay 15, 2014Mice crippled by an autoimmune disease similar to multiple sclerosis (MS) regained the ability to walk and run after a team of researchers led by scientists at The Scripps Research Institute (TSRI), University of Utah and University of California (UC), Irvine implanted human stem cells into their injured spinal cords.

Remarkably, the mice recovered even after their bodies rejected the human stem cells. "When we implanted the human cells into mice that were paralyzed, they got up and started walking a couple of weeks later, and they completely recovered over the next several months," said study co-leader Jeanne Loring, a professor of developmental neurobiology at TSRI.

Thomas Lane, an immunologist at the University of Utah who co-led the study with Loring, said he had never seen anything like it. "We've been studying mouse stem cells for a long time, but we never saw the clinical improvement that occurred with the human cells that Dr. Loring's lab provided," said Lane, who began the study at UC Irvine.

The mice's dramatic recovery, which is reported online ahead of print by the journal Stem Cell Reports, could lead to new ways to treat multiple sclerosis in humans.

"This is a great step forward in the development of new therapies for stopping disease progression and promoting repair for MS patients," said co-author Craig Walsh, a UC Irvine immunologist.

Stem Cell Therapy for MS

MS is an autoimmune disease of the brain and spinal cord that affects more than a half-million people in North America and Europe, and more than two million worldwide. In MS, immune cells known as T cells invade the upper spinal cord and brain, causing inflammation and ultimately the loss of an insulating coating on nerve fibers called myelin. Affected nerve fibers lose their ability to transmit electrical signals efficiently, and this can eventually lead to symptoms such as limb weakness, numbness and tingling, fatigue, vision problems, slurred speech, memory difficulties and depression.

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Stem cell therapy shows promise for MS in mouse model

Stem cell therapy can be defined as a part of a group of new techniques, or technologies that rely on replacing diseased or dysfunctional cells with healthy, functioning ones. These new techniques are being applied experimentally to a wide range of human disorders, including many types of cancer, neurological diseases such as Parkinson's disease and ALS (Lou Gehrig's disease), spinal cord injuries, and diabetes.

Coalition for the Advancement of Medical Research The Coalition for the Advancement of Medical Research (CAMR) is comprised of nationally-recognized patient organizations, universities, scientific societies, foundations, and individuals with life-threatening illnesses and disorders, advocating for the advancement of breakthrough research and technologies in regenerative medicine - including stem cell research and somatic cell nuclear transfer - in order to cure disease and alleviate suffering.

Portraits of Hope Volunteer group of patients and their families and friends who believe that stem cell research has the potential to save the lives of those afflicted by many medical conditions, including spinal cord injury. Purpose is to show the faces and recount the stories of people who have such illnesses and present these "portraits" to federal and state legislators in request for government support.

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Stem Cells & Spinal Cord Injuries

Content by UTS

UTS researchers are experimenting with spinal cord tissue.

It all started at a symposium five years ago. Catherine Gorrie, an expert in spinal cord injury, was listening to a presentation about the differences between the developing brains of children and the mature ones of adults when she had an aah-haa moment.

I began to wonder if there is something in the spines of children that could be manipulated for repair, says Dr Gorrie, a neuroscientist at the University of Technology, Sydney (UTS). It made sense. Dr Gorrie already knew that the more adaptable, or plastic, spinal cords of infants responded more efficiently to injury than did those of adults.

If she could tease out the factors that encouraged generic cells, so-called stem cells, in the spines of newborns to become new nerve cells, neurones, Dr Gorrie reasoned that it should be possible to mimic the process and help repair spinal cord injuries in people of all ages. That would be incredibly important because, to date, there is no cure for spinal cord injury and no proven drug treatment.

The most effective treatments available involve the surgical stabilisation of the spinal column and extensive physical therapy to provide some functional improvement, Dr Gorrie says. There is nothing else.

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In Australia, about 10,000 people live with spinal cord injury and 300-400 new cases emerge every year. Most injuries are a result of car accidents, sporting activities or severe falls.

Childhood spinal cord injury is frequently the result of tumours that compress the spine, crushing neurones which transmit signals to and from the brain.

As the notion of exploiting the biomechanical properties of infant spinal cords took shape in her mind, Dr Gorrie pulled together a team of UTS researchers: Dr Matt Padula, Dr Hui Chen and doctoral students Thomas Cawsey and Yilin Mao.

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Newborns a hope for spinal injuries

Bone Marrow Stem Cells

Dr. Steenblock performing a bone marrow stem cell treatment

The latest discovery in the world of natural medical therapies is STEM CELLS!

You have within you a powerful set of tools to repair your body and keep you healthy. The future of medicine is NOT better drugs but better use and application of your bodys own stem cells. As of now stem cell-rich tissue can be extracted from your hip with virtually no discomfort and used to help restore your body. This opens up an exciting new horizon in terms of preventing and treating disease and tackling the symptoms of aging if not aging itself. Already, patients are returning to Dr. Steenblock for additional bone marrow treatments because they are seeing that their gray or white hair is turning back to its original color. Their skin not infrequently looks younger too and they report having more energy and less arthritic aches and pains!

Over the past six years, Dr. Steenblock and his medical team have done over 2,000 bone marrow procedures with much success. Contrary to the conventional painful methods used, he and his colleagues have developed an almost painless approach to extract bone marrow and the hidden trove of stem cells contained within. Using the patients own bone marrow rather than someone elses has totally eliminated the risk of graft versus host disease and the need for toxic chemotherapy to suppress the immune system. Since Dr. Steenblock is merely transferring stem cells from a persons bones into their blood stream there is never an allergic or rejection type of reaction since these are the patients own cells. The results have at times been phenomenal especially for those under 40 and for those who are really physically fit and walk or run a lot every day. The stronger an individuals bones are the better the bone marrow stem cells are. Even children that are paralyzed and who do not put weight on their legs are generally not going to have good results unless add another facet is added to their treatment. For those people who do not walk much, are not physically fit and who are older than 40, Dr. Steenblock generally recommends that they undergo five successive daily injections of a natural bone marrow mobilizer called Neupogen (Filgrastim) beginning 19 days before they come to his office for their bone marrow treatment(s). The ideal treatment for anyone with a complicated health issue is to first have certain tests done to determine if they have any problems that could interfere with the treatments success. These tests include standard blood tests for anemia, hormones, metabolism, infections, autoimmunity, inflammation and special tests for heavy metal poisons and intestinal infections and infestations. If problems are discovered with these tests then the underlying problem should be corrected before beginning the process of using the Neupogen and the scheduling of the bone marrow treatment(s). The word marrows is pleural intentionally because a person in general has a better result if more stem cells are given. By having two bone marrow procedures on successive days an individual will double the number of stem cells they receive. For example, if a 60 year old sedentary person comes in and does only one bone marrow treatment Dr. Steenblock will generally extract about 400 milliliters of stem cell-rich bone marrow (buffy coat after centrifugation) which is put directly back into the blood stream by intravenous means. The number of active, healthy stem cells in this simple procedure may only be 100 million and these in general will not be as healthy or as active as they will be if the patient first has any known or potential impediments to their post-infusion activity eliminated and they are given the 5 daily injections of Neupogen. When a person comes to the clinic 14 days after their last Neupogen injection, that same 400 ml of bone marrow will have somewhere between 500 and 1000 million stem cells and then if they repeat the process the next day they will get another 500-1000 million stem cells. By this combination of eradicating infections, correcting other problems discovered using our testing, and then using Neupogen followed by two bone marrow treatments patients will be receiving well over a billion stem cells.

Benefits of Bone Marrow Stem Cells

What is the secret behind the successes Dr. Steenblock has seen with the bone marrow treatments? While bone marrow transplants have been done for the past 50 years for cancer patients and those with blood disorders, the whole bone marrow procedure done by Dr. Steenblock is different because it is so SIMPLE! He uses a persons own bone marrow and instead of isolating one type of stem cell, he takes and uses the whole raw bone marrow which contains a rich variety of stem and progenitor cells. In fact, bone marrow is rich in two different types of stem cells: One type turns into blood cells, blood vessels, and cells of the immune system and are called hematopoietic stem cells (heme meaning blood-related). The other type of stem cell is the support (stromal or mesenchymal) stem cell that produces bone, fat, tendons, skin, muscles and connective tissue. Recent research shows that these hematopoietic and the support stem cells are also able to divide into all types of brain cells, including glial cells (white matter) and neurons (gray matter). The bone marrow also contains retinal progenitor cells and several patients have actually commented on how their vision improved as a side benefit of their bone marrow procedure. These two type of stem cells work better together in a ratio of one hematopoietic to 4 to 8 support (stromal or mesenchymal) stem cells which is the ratio found normally in most peoples bone marrow.

In regard to its anti-aging effects, the bone marrow contains primitive progenitor cells that are associated with the early development of the fetus. These primitive cells reside dormant deep inside each of our bones and sport a virginal profile from early development in that these stem cells are generally resting and not active. This inactivity protects them from chemicals or stresses that induce mutations such as occurs in those bone marrow stem cells that are located in the more superficial areas of the bone which are constantly making red and white blood cells. When these primitive, more pure cells are released into a persons system, there can be a revitalization of the body that physiologically sets the clock back in-a-way since these stem cells get into all parts of the body and produce more growth factors than would otherwise be possible. It is this increase in growth factors that induces the regenerative processes. For those that can afford it Dr. Steenblock uses growth factors oriented toward improving the organs that are diseased. For example, if a patients chief problem is their lungs then he may suggest some lung growth factors to be taken right along with the Neupogen and then continued for 6 weeks to help push the stem cells into becoming more like lung tissue cells.

Bottom line: Bone marrow stem cells have the potential to repair damaged tissues and organs. Whether a person wants an anti-aging treatment or needs the procedure to repair damage in joints, liver, kidneys, heart or brain, bone marrow transplants is an efficient and sure way to flood their body with stem cells.

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Bone Marrow Stem Cells - Dr. Steenblock- Regenerative Medicine

FRESNO, Calif. (KFSN) --

"Grace is what's carried me through this," Minch told Ivanhoe.

Ten years ago, at just 49, the choir singer and her husband were told she would need a quadruple bypass.

"Now we are at the point where my heart is severely damaged and nothing is really helping," Minch said.

Doctors said a heart transplant was her only option, but she'll soon find out if she'll be accepted into a new trial that could use her own stem cells to help repair the once thought irreversible damage, "or even create new blood vessels within areas of the heart that have been damaged," Jon George, MD, Interventional Cardiologist, Temple University School of Medicine, told Ivanhoe.

First, stem cells are taken from a patient's bone marrow. Then using a special catheter and 3D mapping tool, the cells are injected directly into the damaged tissue.

"We have results from animal data that show blood vessels regrow in the patients that actually get stem cell therapy," Dr. George said.

It's a possible answer to Debbie's prayers.

Temple University Hospital is currently pre-screening patients for the trial. For more information, call 215-707-5340.

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Stem Cells to The Rescue: Repairing The Hearts

Harvard scientists have merged stem cell and organ-on-a-chip technologies to grow, for the first time, functioning human heart tissue carrying an inherited cardiovascular disease. The research appears to be a big step forward for personalized medicine because it is working proof that a chunk of tissue containing a patient's specific genetic disorder can be replicated in the laboratory.

The work, published in May 2014 in Nature Medicine, is the result of a collaborative effort bringing together scientists from the Harvard Stem Cell Institute, the Wyss Institute for Biologically Inspired Engineering, Boston Children's Hospital, the Harvard School of Engineering and Applied Sciences, and Harvard Medical School. It combines the organs-on-chips expertise of Kevin Kit Parker, PhD, and stem cell and clinical insights by William Pu, MD.

A release from Harvard explains that using their interdisciplinary approach, the investigators modeled the cardiovascular disease Barth syndrome, a rare X-linked cardiac disorder caused by mutation of a single gene called Tafazzin, or TAZ. The disorder, which is currently untreatable, primarily appears in boys, and is associated with a number of symptoms affecting heart and skeletal muscle function.

The researchers took skin cells from two Barth syndrome patients, and manipulated the cells to become stem cells that carried these patients' TAZ mutations. Instead of using the stem cells to generate single heart cells in a dish, the cells were grown on chips lined with human extracellular matrix proteins that mimic their natural environment, tricking the cells into joining together as they would if they were forming a diseased human heart. The engineered diseased tissue contracted very weakly, as would the heart muscle seen in Barth syndrome patients. The investigators then used genome editinga technique pioneered by Harvard collaborator George Church, PhDto mutate TAZ in normal cells, confirming that this mutation is sufficient to cause weak contraction in the engineered tissue. On the other hand, delivering the TAZ gene product to diseased tissue in the laboratory corrected the contractile defect, creating the first tissue-based model of correction of a genetic heart disease. The release quotes Parker as saying, "You don't really understand the meaning of a single cell's genetic mutation until you build a huge chunk of organ and see how it functions or doesn't function. In the case of the cells grown out of patients with Barth syndrome, we saw much weaker contractions and irregular tissue assembly. Being able to model the disease from a single cell all the way up to heart tissue, I think that's a big advance."

Furthermore, the scientists discovered that the TAZ mutation works in such a way to disrupt the normal activity of mitochondria, often called the power plants of the cell for their role in making energy. However, the mutation didn't seem to affect overall energy supply of the cells. In what could be a newly identified function for mitochondria, the researchers describe a direct link between mitochondrial function and a heart cell's ability to build itself in a way that allows it to contract. "The TAZ mutation makes Barth syndrome cells produce an excess amount of reactive oxygen species or ROSa normal byproduct of cellular metabolism released by mitochondriawhich had not been recognized as an important part of this disease," said Pu, who cares for patients with the disorder. "We showed that, at least in the laboratory, if you quench the excessive ROS production then you can restore contractile function," Pu added. "Now, whether that can be achieved in an animal model or a patient is a different story, but if that could be done, it would suggest a new therapeutic angle." His team is now trying to translate this finding by doing ROS therapy and gene replacement therapy in animal models of Barth syndrome to see if anything could potentially help human patients. At the same time, the scientists are using their human 'heart disease-on-a-chip' as a testing platform for drugs that are potentially under trial or already approved that might be useful to treat the disorder.

"We tried to thread multiple needles at once and it certainly paid off," Parker said. "I feel that the technology that we've got arms industry and university-based researchers with the tools they need to go after this disease." Both Parker and Pu, who first talked about collaborating at a 2012 Stockholm conference, credit their partnership and scientific consilience for the success of this research. Parker asserted that the 'organs-on-chips' technology that has been a flagship of his lab only worked so fast and well because of the high quality of Pu's patient-derived cardiac cells. "When we first got those cells down on the chip, Megan, one of the joint first authors, texted me 'this is working,'" he recalled. "We thought we'd have a much harder fight." "When I'm asked what's unique about being at Harvard, I always bring up this story," Pu said. "The diverse set of people and cutting-edge technology available at Harvard certainly made this study possible." The researchers also involved in this work include: Joint first authors Gang Wang, MD, of Boston Children's Hospital, and Megan McCain, PhD, who earned her degree at the Harvard School of Engineering and Applied Sciences and is now an assistant professor at the University of Southern California. Amy Roberts, MD, of Boston Children's Hospital, and Richard Kelley, MD, PhD, at the Kennedy Krieger Institute provided patient data and samples, and Frdric Vaz, PhD, and his team at the Academic Medical Center in the Netherlands conducted additional analyses. Technical protocols were shared by Kenneth Chien, MD, PhD, at the Karolinska Institutet.

Kevin Kit Parker, PhD, is the Tarr Family Professor of Bioengineering and Applied Physics in Harvard's School of Engineering and Applied Sciences, a Core Faculty member of the Wyss Institute for Biologically Inspired Engineering, and a Principal Faculty member of the Harvard Stem Cell Institute. William Pu, MD, is an Associate Professor at Harvard Medical School, a member of the Department of Cardiology at Boston Children's Hospital, and an Affiliated Faculty member of the Harvard Stem Cell Institute. George Church, PhD, is a Professor of Genetics at Harvard Medical School and a Core Faculty member of the Wyss Institute of Biologically Inspired Engineering. The work was supported by the Barth Syndrome Foundation, Boston Children's Hospital, the National Institutes of Health, and charitable donations from Edward Marram, Karen Carpenter, and Gail Federici Smith.

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Stem Cells Make Heart Disease-on-a-Chip

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