Endothelial cells residing in the coronary arteries can function as cardiac stem cells to produce new heart muscle tissue, Vanderbilt University investigators have discovered.

The findings, published recently in Cell Reports, offer insights into how the heart maintains itself and could lead to new strategies for repairing the heart when it fails after a heart attack.

The heart has long been considered to be an organ without regenerative potential, said Antonis Hatzopoulos, Ph.D., associate professor of Medicine and Cell and Developmental Biology.

"People thought that the same heart you had as a young child, you had as an old man or woman as well," he said.

Recent findings, however, have demonstrated that new heart muscle cells are generated at a low rate, suggesting the presence of cardiac stem cells. The source of these cells was unknown.

Hatzopoulos and colleagues postulated that the endothelial cells that line blood vessels might have the potential to generate new heart cells. They knew that endothelial cells give rise to other cell types, including blood cells, during development.

Now, using sophisticated technologies to "track" cells in a mouse model, they have demonstrated that endothelial cells in the coronary arteries generate new cardiac muscle cells in healthy hearts. They found two populations of cardiac stem cells in the coronary arteries -- a quiescent population in the media layer and a proliferative population in the adventitia (outer) layer.

The finding that coronary arteries house a cardiac stem cell "niche" has interesting implications, Hatzopoulos said. Coronary artery disease -- the No. 1 killer in the United States -- would impact this niche.

"Our study suggests that coronary artery disease could lead to heart failure not only by blocking the arteries and causing heart attacks, but also by affecting the way the heart is maintained and regenerated," he said.

The current research follows a previous study in which Hatzopoulos and colleagues demonstrated that after a heart attack, endothelial cells give rise to the fibroblasts that generate scar tissue.

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Coronary arteries hold heart-regenerating cells

PUBLIC RELEASE DATE:

20-Aug-2014

Contact: Craig Boerner craig.boerner@vanderbilt.edu 615-322-4747 Vanderbilt University Medical Center

Endothelial cells residing in the coronary arteries can function as cardiac stem cells to produce new heart muscle tissue, Vanderbilt University investigators have discovered.

The findings, published recently in Cell Reports, offer insights into how the heart maintains itself and could lead to new strategies for repairing the heart when it fails after a heart attack.

The heart has long been considered to be an organ without regenerative potential, said Antonis Hatzopoulos, Ph.D., associate professor of Medicine and Cell and Developmental Biology.

"People thought that the same heart you had as a young child, you had as an old man or woman as well," he said.

Recent findings, however, have demonstrated that new heart muscle cells are generated at a low rate, suggesting the presence of cardiac stem cells. The source of these cells was unknown.

Hatzopoulos and colleagues postulated that the endothelial cells that line blood vessels might have the potential to generate new heart cells. They knew that endothelial cells give rise to other cell types, including blood cells, during development.

Now, using sophisticated technologies to "track" cells in a mouse model, they have demonstrated that endothelial cells in the coronary arteries generate new cardiac muscle cells in healthy hearts. They found two populations of cardiac stem cells in the coronary arteries a quiescent population in the media layer and a proliferative population in the adventitia (outer) layer.

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Vanderbilt researchers find that coronary arteries hold heart-regenerating cells

ROCHESTER, Minn. (KTTC) -- Medical officials are talking about a breakthrough clinical trial that could help the heart repair itself.

On Tuesday afternoon, Mayo Clinic and Cardio3 BioSciences officials outlined an FDA-approved clinical trial to be carried out in the United States. A similar trial has already been underway in Europe.

Cardio3 CEO Christian Homsy said stem cells are a major part of this heart-healing process. "What we do is take cells from a patient and we reprogram those cells to become cardiac reparative cells. Those cells have the ability to come and repair the heart." Those stem cells would come from the bone marrow of patients who suffer from heart failure.

This treatment is the result of a Mayo Clinic discovery. In Mayo's breakthrough process, stem cells that are harvested from a cardiac patient's bone marrow undergo a guided treatment designed to improve heart health in people suffering from heart failure.

Cardio3 officials said a manufacturing facility will be the first thing that is needed for this clinical trial, and the rest of the details like staffing will follow.

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Trial to use stem cells to repair heart

Chemotherapy and Radiation Therapy

Before you get the stem cell transplant, youll get the actual cancer treatment. To destroy the abnormal stem cells, blood cells, and cancer cells your doctor will give you high doses of chemotherapy, radiation therapy, or both. In the process, the treatment will kill healthy cells in your bone marrow, essentially making it empty. Your blood counts (number of red blood cells, white blood cells, and platelets) will drop quickly. Since chemotherapy and radiation can cause nausea and vomiting, you might need anti-nausea drugs.

Without bone marrow, your body is vulnerable. You won't have enough white blood cells to protect you from infection. So during this time, you might be isolated in a hospital room or required to stay at home until the new bone marrow starts growing. You might also need transfusions and medication to keep you healthy.

A few days after youve finished with your chemotherapy or radiation treatment, your doctor will order the actual stem cell transplant. The harvested stem cells -- either from a donor or from your own body -- are thawed and infused into a vein through an IV tube. The process is essentially painless. The actual stem cell transplant is similar to a blood transfusion. It takes one to five hours.

The stem cells then naturally move into the bone marrow. The restored bone marrow should begin producing normal blood cells after several days, or up to several weeks later.

The amount of time youll need to be isolated will depend on your blood counts and general health. When you are released from the hospital or from isolation at home, your transplant team will provide you with specific instructions on how to care for yourself and prevent infections. Youll also learn what symptoms need to be checked out immediately. Full recovery of the immune system might take months or even years. Your doctor will need to do tests to check on how well your new bone marrow is doing.

There are also variations in the stem cell transplant process being studied in clinical trials. One approach is called a tandem transplant, in which a person would get two rounds of chemotherapy and two separate stem cell transplants. The two transplants are usually done within six months of one another.

Another is called a mini-transplant, in which doctors use lower doses of chemotherapy and radiation. The treatment is not strong enough to kill all of the bone marrow -- and it wont kill all of the cancer cells either. However, once the donated stem cells take hold in the bone marrow, they produce immune cells that might attack and kill the remaining cancer cells. This is also called a non-myeloablative transplant.

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Bone Marrow Transplants and Stem Cell Transplants for ...

A team of chemical engineers from MIT has developed a new method of stimulating bone growth, by utilizing the same chemical processes that occur naturally in the human body following an injury such as a broken or fractured bone. The technique involves the insertion of a porous scaffold coated with growth factors that prompt the body's own cells to naturally mend the damaged or deformed bone.

Current techniques for replacing or mending damaged bone often include a bone transplant from another area of the patient's body. This is an expensive, painful, and often inadequate option for treatment, as it is difficult to harvest enough bone to successfully treat the wound. Due to the inadequacies of the current forms of bone replacement treatment, a number of scaffold-based approaches are in development, however few are as promising as the tissue scaffold presented by the team from MIT.

The new method would seek to mimic the natural steps taken by the human body to encourage bone growth without the unpleasant necessity of extracting further bone from the patient's body. After a break or fracture, the body releases both platelet-derived growth factors, (PDGF) and bone morphogenetic protein 2 (BMP-2), in order to stimulate natural bone regeneration. These factors essentially recruit other immature cells, coaxing them to become osteoblasts, a cell type with the capacity to create new bone. At the same time, the PDFG and BMP-2 provide a supporting structure around which the bone can be rebuilt.

The 0.1 mm-thick polymer scaffold sheet developed by the scientists from MIT would appear to successfully mimic this biological process, releasing the growth factors in the correct order and quantity, essentially tricking the body into thinking it had initiated the healing process itself. Previous attempts at biomimicry in this area have failed due to an inability to release the growth factors in a natural and controlled fashion, causing the body to clear the factors away from the wound before they could have any substantial healing effect.

The scaffold has the potential to do away with the painful, invasive procedures currently used to repair/replace bone (Image: MIT)

"You want the growth factor to be released very slowly and with nanogram or microgram quantities, not milligram quantities," States Paula Hammond, member of MIT's Koch Institute for Integrative Cancer Research and Department of Engineering, and senior author on the paper outlining the results of the study. "You want to recruit these native adult stem cells we have in our bone marrow to go to the site of injury and then generate bone around the scaffold, and you want to generate a vascular system to go with it."

The measured release of growth factors is achieved by layering the porous scaffold with around 40 layers of BMP-2, followed by another 40 layers of PDGF. Once the layering process is complete, medical practitioners can cut out segments of the scaffold, tailoring the treatment to fit any size of wound. Furthermore, once the treatment has run its course and the bone has been regrown, the biodegradable scaffold is safely adsorbed into the body, leaving no harmful traces as a by-product of the procedure.

The scaffold has been tested in the lab by administering the treatment to rats with skull deficiencies too large to be healed without the aid of outside stimuli. It was found that the initial release of the PDGF created a healing cascade, mobilizing cells important to the rebuilding process to move to the site of the deformity. The BMP-2 then went to work inducing a number of the cells to become osteoblasts, which would go on to create the new bone.

Only two weeks after the initial transplant, it was found that fresh bone had been created that was indistinguishable in nature from the natural bone found in the surrounding areas of the skull. Looking to the future, the team hopes to test the technique on larger animals, with the long-term goal of advancing to clinical trials.

A paper covering the research carried out by the team from MIT has been published in the journal Proceedings of the National Academy of Sciences of the United States of America.

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MIT scientists use polymer scaffold to stimulate bone growth

Novartis ( NVS ) recently entered into an investment and option agreement with Israel-based Gamida Cell, a company which focuses on stem cell expansion technologies and therapeutic products.

As per the terms of the agreement, Novartis will invest $35 million in Gamida Cell. In exchange, Novartis will receive a 15% stake in Gamida Cell and an option to fully acquire the company.

The option for full acquisition is exercisable for a limited period of time following achievement of certain milestones in connection with the development of pipeline candidate, NiCord. These milestones are expected to be achieved during 2015. Novartis will also be required to pay the other shareholders in Gamida Cell approximately $165 million upon exercising the option along with potential milestone payments of $435 million.

We note that Gamida Cell is developing stem cell therapy for the potential treatment of blood cancers, solid tumors, non-malignant hematological diseases such as sickle cell disease and thalassemia, neutropenia and acute radiation syndrome, autoimmune diseases and genetic metabolic diseases as well as conditions that can be helped by regenerative medicine.

The company is currently evaluating NiCord for the potential treatment of hematological malignancies such as leukemia and lymphoma in a phase I/II study using its proprietary NAM technology.

Meanwhile, enrolment is on for the company's phase I/II study on NiCord for pediatric sickle cell disease.

We remind investors that Novartis has been taking strategic steps to realign its portfolio in order to focus on its core portfolio of pharmaceuticals, eye care and generics. Novartis' recent deal to acquire oncology products from GlaxoSmithKline ( GSK ) and the divestiture of the Vaccines business is a step in the right direction.

Novartis, a large-cap pharma, currently carries a Zacks Rank #3 (Hold). Right now, Allergan ( AGN ) and AbbVie ( ABBV ) look well positioned among the large-cap pharmas. While Allergan carries a Zacks Rank #1 (Strong Buy), AbbVie is a Zacks Rank #2 (Buy) stock.

NOVARTIS AG-ADR (NVS): Free Stock Analysis Report

ABBVIE INC (ABBV): Free Stock Analysis Report

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Novartis to Invest $35M in Gamida Cell for 15% Equity - Analyst Blog

(PRWEB UK) 21 August 2014

The success of stem cell medicine does not depend on funding alone

Funding is of the upmost importance but access to the right material is vital.

Stem Cell Banking of a childs own stem cells for potentially a lifetime of use, is a way of storing their health for their future. So it is vital that the right stem cells are available for treatment when they are needed at any time in their life.

Tony Veverka, Group CEO of specialist stem cell bank BioEden says, "Funding is of the upmost importance so that research can continue, but access to the right material is vital."

Gaining access to the right material for stem cell therapy has dramatically simplified since BioEden pioneered an entirely non-invasive method of taking stem cells from children's baby teeth. No longer is there just the option of stem cells from embryos, bone marrow or cord blood, but the option of taking quality cells from the baby tooth after it has fallen out naturally.

BioEden believes it can cut NHS funding dramatically by individuals banking their own stem cells, and they continue to call for clarity and transparency so that a prolonged and healthier life is accessible to all. http://www.thetimes.co.uk/tto/business/industries/health/article4181168.ece

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The Times Have Published Only Half the Story, Says Specialist Stem Cell Bank BioEden

By Estel Grace Masangkay

With help from the zebrafish, a team of Australian researchers has uncovered how hematopoietic stem cells (HSC) renew themselves, considered by many to be the holy grail of stem cell research.

HSCs are a significant type of stem cell present in the blood and bone marrow. These are needed for the replenishment of the bodys supply of blood and immune cells. HSCs already play a part in transplants in patients with blood cancers such as leukemia and myeloma. The stem cells are also studied for their potential to transform into vital cells including muscle, bone, and blood vessels.

Understanding how HSCs form and renew themselves has potential application in the treatment of spinal cord injuries, degenerative disorders, even diabetes. Professor Peter Currie, of the Australian Regenerative Medicine Institute at Victorias Monash University, led a research team to discover a crucial part of HSCs development. Using a high-resolution microscopy, Prof. Curies team caught HSCs on film as they formed inside zebrafish embryos. The discovery was made while the researchers were studying muscle mutations in the aquatic animal.

Zebrafish make HSCs in exactly the same way as humans do, but whats special about these guys is that their embryos and larvae develop free living and not in utero as they do in humans. So not only are these larvae free-swimming, but they are also transparent, so we could see every cell in the body forming, including HSCs, explained Prof. Currie.

While playing the film back, the researchers noticed that a buddy cell came along to help the HSCs form. Called endotome cells, they aided pre-HSCs to turn into HSCs. Prof. Currie said, Endotome cells act like a comfy sofa for pre-HSCs to snuggle into, helping them progress to become fully fledged stem cells. Not only did we identify some of the cells and signals required for HSC formation, we also pinpointed the genes required for endotome formation in the first place.

The next step for the researchers is to locate the signals present in the endotome cells that trigger HSC formation in the embryo. This can help scientists make different blood cells on demand for blood-related disorders. Professor Currie also pointed out the discoverys potential for correcting genetic defects in the cell and transplanting them back in the body to treat disorders.

The teams work was published in the international journal Nature.

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Stem Cell Research Holy Grail' Uncovered, Thanks to Zebrafish

Ruxolitinib (trade name: Jakavi) has been approved since August 2012 for the treatment of adults with myelofibrosis. In an early benefit assessment pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether this new drug offers an added benefit over the appropriate comparator therapy specified by the Federal Joint Committee (G-BA).

According to the results, there is an indication of considerable added benefit in comparison with "best supportive care" (BSC) because ruxolitinib is better at relieving symptoms. Moreover, a hint of an added benefit with regard to survival can be derived from the dossier. Its extent is non-quantifiable, however.

Bone marrow is replaced by connective tissue

Myelofibrosis is a rare disease of the bone marrow, in which the bone marrow is replaced by connective tissue. As a consequence of this so-called fibrosis, the bone marrow is no longer able to produce enough blood cells. Sometimes the spleen or the liver takes over some of the blood production. Then these organs enlarge and can cause abdominal discomfort and pain. The typical symptoms also include feeling of fullness, night sweats and itching. Some patients with myelofibrosis develop leukemia.

Stem cell transplantation is currently the only option to cure myelofibrosis. The drug ruxolitinib aims to relieve the symptoms of myelofibrosis.

G-BA specifies appropriate comparator therapy

Ruxolitinib is an option for patients with so-called primary or secondary myelofibrosis whose spleen is already enlarged (splenomegaly) or who have other disease-related symptoms.

The G-BA specified "best supportive care" (BSC) as appropriate comparator therapy. BSC means a therapy that provides the patient with the best possible, individually optimized, supportive treatment to alleviate symptoms and improve quality of life. This also includes adequate pain therapy.

Relevant study ongoing until 2015

In its assessment, IQWiG could include one randomized controlled trial (RCT) conducted in 89 centres in Australia, Canada and the United States (COMFORT-I). The 309 patients in total were either treated with ruxolitinib plus BSC or with placebo plus BSC.

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Ruxolitinib for myelofibrosis: Indication of considerable added benefit

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Newswise A new study by Barbara Beltz, the Allene Lummis Russell Professor of Neuroscience at Wellesley College, and Irene Sderhll of Uppsala University, Sweden, published in the August 11 issue of the journal Developmental Cell, demonstrates that the immune system can produce cells with stem cell properties, using crayfish as a model system. These cells can, in turn, create neurons in the adult animal. The flexibility of immune cells in producing neurons in adult animals raises the possibility of the presence of similar types of plasticity in other animals.

We have been suspicious for some time that the neuronal precursor cells (stem cells) in crayfish were coming from the immune system, Beltz wrote. The paper contains multiple lines of evidence that support this conclusion, in addition to the experiments showing that blood cells transferred from a donor to a recipient animal generate neurons.

Beltz, whose research focuses on the production of new neurons in the adult nervous system, uses the crustacean brain as the model system because the generations of precursor cells are spatially segregated from one another. According to Beltz, this separation is crucial because it allowed the researchers to determine that the first generation precursors do not self-renew. For the Developmental Cell study, the cells of one crayfish were labeled and this animals blood was used for transfusions into another crayfish. They found that the donor blood cells could generate neurons in the recipient.

In many adult organisms, including humans, neurons in some parts of the brain are continually replenished. While this process is critical for ongoing health, dysfunctions in the production of new neurons may also contribute to several neurological diseases, including clinical depression and some neurodegenerative disorders.

Beltz notes, of course, that it is difficult to extrapolate from crayfish to human disease. However, because of existing research suggesting that stem cells harvested from bone marrow also can become neural precursors and generate neurons, she says it is tempting to suggest that the mechanism proposed in crayfish may also be applicable in evolutionarily higher organisms, perhaps even in humans.

Prior studies conducted in both humans and mice and published about a decade ago, showed that bone marrow recipients who had received a transplant from the opposite gender had neurons with the genetic signature of the opposite sex. The implication was that cells from the bone marrow generated those neurons. However, it is currently thought that neuronal stem cells in mammals, including humans, are self-renewing and therefore do not need to be replenished. Thus, these findings have not been interpreted as contributing to a natural physiological mechanism.

Every experiment we did confirmed the close relationship between the immune system and adult neurogenesis, Beltz said. Often when one is doing research, experiments can be fussy or give variable results. But for this work, once we started asking the right questions, the experiments worked first time and every time. The consistency and strength of the data are remarkable.

Our findings in crayfish indicate that the immune system is intimately tied to mechanisms of adult neurogenesis, suggesting a much closer relationship between the immune system and nervous system than has been previously appreciated, said Sderhll. If further studies demonstrate a similar relationship between the immune system and brain in mammals, these findings would stimulate a new area of research into immune therapies to target neurological diseases.

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Blood Cells Generate Neurons in Crayfish; Could Have Implications for Treatment of Neurodegenerative Disorders

A new research has suggested that immune cells, known as natural killer cells could help in hunting down and kill cancers that have spread in the body.

The study showed that a protein called MCL-1 was vital for survival of natural killer cells.

Dr. Nick Huntington said that they discovered that MCL-1 was absolutely essential for keeping natural killer cells alive and without natural killer cells, the body was unable to destroy melanoma metastases that had spread throughout the body, and the cancers overwhelmed the lungs.

Huntington said that the natural killer cells led the response that caused rejection of donor stem cells in bone marrow transplantations and they also produced inflammatory signals that could result in toxic shock syndrome, a potentially fatal illness caused by bacterial toxins that causes a whole-body inflammatory reaction.

The study is published in the journal Nature Communications.

(Posted on 15-08-2014)

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'Killer' immune cells destroy body cancer

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Newswise A genetic variation linked to schizophrenia, bipolar disorder and severe depression wreaks havoc on connections among neurons in the developing brain, a team of researchers reports. The study, led by Guo-li Ming, M.D., Ph.D., and Hongjun Song, Ph.D., of the Johns Hopkins University School of Medicine and described online Aug. 17 in the journal Nature, used stem cells generated from people with and without mental illness to observe the effects of a rare and pernicious genetic variation on young brain cells. The results add to evidence that several major mental illnesses have common roots in faulty wiring during early brain development.

This was the next best thing to going back in time to see what happened while a person was in the womb to later cause mental illness, says Ming. We found the most convincing evidence yet that the answer lies in the synapses that connect brain cells to one another.

Previous evidence for the relationship came from autopsies and from studies suggesting that some genetic variants that affect synapses also increase the chance of mental illness. But those studies could not show a direct cause-and-effect relationship, Ming says.

One difficulty in studying the genetics of common mental illnesses is that they are generally caused by environmental factors in combination with multiple gene variants, any one of which usually could not by itself cause disease. A rare exception is the gene known as disrupted in schizophrenia 1 (DISC1), in which some mutations have a strong effect. Two families have been found in which many members with the DISC1 mutations have mental illness.

To find out how a DISC1 variation with a few deleted DNA letters affects the developing brain, the research team collected skin cells from a mother and daughter in one of these families who have neither the variation nor mental illness, as well as the father, who has the variation and severe depression, and another daughter, who carries the variation and has schizophrenia. For comparison, they also collected samples from an unrelated healthy person. Postdoctoral fellow Zhexing Wen, Ph.D., coaxed the skin cells to form five lines of stem cells and to mature into very pure populations of synapse-forming neurons.

After growing the neurons in a dish for six weeks, collaborators at Pennsylvania State University measured their electrical activity and found that neurons with the DISC1 variation had about half the number of synapses as those without the variation. To make sure that the differences were really due to the DISC1 variation and not to other genetic differences, graduate student Ha Nam Nguyen spent two years making targeted genetic changes to three of the stem cell lines.

In one of the cell lines with the variation, he swapped out the DISC1 gene for a healthy version. He also inserted the disease-causing variation into one healthy cell line from a family member, as well as the cell line from the unrelated control. Sure enough, the researchers report, the cells without the variation now grew the normal amount of synapses, while those with the inserted mutation had half as many.

We had our definitive answer to whether this DISC1 variation is responsible for the reduced synapse growth, Ming says.

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Stem Cells Reveal How Illness-Linked Genetic Variation Affects Neurons

ALAMEDA, Calif.--(BUSINESS WIRE)--BioTime, Inc. (NYSE MKT: BTX) today reported financial results for the first quarter ended June 30, 2014 and highlighted recent corporate accomplishments.

We are pleased with our success to date in building toward our goal of developing both near-term commercial applications of our technologies and maintaining our focus on the power of pluripotent stem cells to create innovative human therapeutics, said Dr. Michael D. West, BioTimes Chief Executive Officer. Near-term product development underway includes our subsidiary OncoCyte Corporations three cancer diagnostic products undergoing clinical studies, mobile health product development in our subsidiary LifeMap Solutions, Inc., our Renevia pivotal clinical trial in Europe, steps to prepare for the marketing of our recently FDA-cleared wound healing product Premvia, and growing research product sales by our ESI BIO division.

BioTimes longer-term major therapeutic product opportunities are based on the broad range of cell-based regenerative therapies planned for development from its pluripotent stem cell technology platform. This platform is protected by over 600 patents and patent applications worldwide within the BioTime family of companies. Our subsidiary Asterias Biotherapeutics, Inc. has submitted an amended IND to the FDA for a Phase 1/2a clinical trial of AST-OPC1 for the treatment of cervical spinal cord injury and is currently awaiting clearance from the FDA for that trial. Asterias is also currently undertaking process development of AST-VAC2, a cancer immunotherapy targeting the important antigen called telomerase, for a potential clinical trial in lung cancer. This progress, along with the appointment of Pedro Lichtinger as Asterias CEO and the award of a $14 million grant from the California Institute for Regenerative Medicine, should fuel the development of these first-in-class therapeutic products. Recently, Asterias shares began to trade publicly under the symbol ASTYV, the first of our subsidiaries to have its shares trade publicly. Lastly, we expect that BioTimes subsidiary Cell Cure Neurosciences Ltd. will soon file its IND to begin a clinical trial of OpRegen for the treatment of age-related macular degeneration. Additional important cell-based product development is underway in our disease-focused subsidiaries OrthoCyte Corporation and ReCyte Therapeutics.

As we saw in the first quarter of this year, our expenses have risen compared to recent quarters, but our progress during the second quarter in streamlining our workforce through shared core resources among our subsidiaries should reduce our cash burn rate in the third quarter. We would like to thank those who share our goal of better health in the coming era of regenerative medicine. Their continued support and the diligent efforts of our collaborators at leading academic medical institutions is critical in advancing our products from the lab bench to the clinic, where they are desperately needed.

Second Quarter and Recent Highlighted Corporate Accomplishments

Financial Results

Revenue

For the six months ended June 30, 2014, on a consolidated basis, total revenue was $2.2 million, up $0.3 million or 19% from $1.8 million for the same period one year ago. The increase in revenue is primarily attributable to a $0.4 million increase in grant income primarily from a grant awarded to BioTimes subsidiary Cell Cure Neurosciences Ltd. (Cell Cure Neurosciences) from Israels Office of the Chief Scientist, offset in part by the decline in license fees of $0.1M primarily due to full recognition of the unamortized balance of the Summit license fees received in advance during the fourth quarter of 2013 as a result of the termination of our license agreements with Summit in 2013.

Expenses

Operating expenses for the six months ended June 30, 2014 were $26.0 million, compared to expenses of $18.0 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, including additional expenses in the Renevia clinical safety trial program, the development of OpRegen by BioTimes subsidiary Cell Cure Neurosciences for the treatment of dry age related macular degeneration, and the increased staffing and operations of Asterias in connection with the Geron stem cell asset acquisition and by LifeMap Solutions. In addition, during the first six months in 2014, operating expenses included $1.5 million of amortization expense of intangible assets recorded in connection with the Geron stem cell asset acquisition in October 2013.

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BioTime Announces Second Quarter 2014 Results and Recent Developments

In a boon to stem cell research and regenerative medicine, scientists at Boston Children's Hospital, the Wyss Institute for Biologically Inspired Engineering at Harvard University and Boston University have created a computer algorithm called CellNet as a "roadmap" for cell and tissue engineering, to ensure that cells engineered in the lab have the same favorable properties as cells in our own bodies. CellNet and its application to stem cell engineering are described in two back-to-back papers in the August 14 issue of the journal Cell.

Scientists around the world are engaged in culturing pluripotent stem cells (capable of forming all the body's tissues) and transforming them into specialized cell types for use in research and regenerative medicine. Available as an Internet resource for any scientist to use, CellNet provides a much needed "quality assurance" measure for this work.

The two papers also clarify uncertainty around which methods are best for stem cell engineering, and should advance the use of cells derived from patient tissues to model disease, test potential drugs and use as treatments. For example, using CellNet, one of the studies unexpectedly found that skin cells can be converted into intestinal cells that were able to reverse colitis in a mouse model.

"To date, there has been no systematic means of assessing the fidelity of cellular engineering -- to determine how closely cells made in a petri dish approximate natural tissues in the body," says George Q. Daley, MD, PhD, Director of the Stem Cell Transplantation Program at Boston Children's and senior investigator on both studies. "CellNet was developed to assess the quality of engineered cells and to identify ways to improve their performance."

Gene Signatures

CellNet applies network biology to discover the complex network of genes that are turned on or off in an engineered cell, known as the cell's Gene Regulatory Network or GRN. It then compares that network to the cell's real-life counterpart in the body, as determined from public genome databases. Through this comparison, researchers can rigorously and reliably assess:

"CellNet will also be a powerful tool to advance synthetic biology -- to engineer cells for specific medical applications," says James Collins, PhD, Core Faculty member at the Wyss Institute and the William F. Warren Distinguished Professor at Boston University, co-senior investigator on one of the studies.

Putting CellNet to the Test

The researchers -- including co-first authors Patrick Cahan, PhD and Samantha Morris, PhD, of Boston Children's, and Hu Li, PhD, of the Mayo Clinic, first used CellNet to assess the quality of eight kinds of cells created in 56 published studies.

In a second study, they applied CellNet's teachings to a recurring question in stem cell biology: Is it feasible to directly convert one specialized cell type to another, bypassing the laborious process of first creating an iPS cell? This study looked at two kinds of directly converted cells: liver cells made from skin cells, and macrophages made from B cells.

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Tissue development 'roadmap' created to guide stem cell medicine

Immunologist Nick Huntington. Photo: Getty Images/Paul Jeffers

The bodys natural killer cells, as their Hollywood-style name suggests, are key to the immune system. They are programmed to hunt out and destroy foreign and diseased cells. But they dont always identify their targets. When this happens, diseases such as cancer can set in.

But a team of researchers at the Walter and Eliza Hall Institute of Medical Research have worked out what the group of highly specialised killer cells need to function at their best. Its a protein called MCL-1.

Immunologist Nick Huntington said the protein was effectively a switch which could turn the killer cells on or off.

The discovery, outlined on Thursday in the journal Nature Communications, opens the way for new drug treatments to tame the spread of a range of diseases, including cancer.

It could also assist patients who undergo donor stem cell or bone marrow transplants - because by manipulating the killer cells switch, foreign bodies such as stem cells could go unchallenged by the bodys immune system.

"Its the only protein which does this in the cell, Dr Huntington said. It needs to be turned on for the cell to survive and when its turned off the cell will die.

While aware of the existence of the MCL-1 protein and its importance at a fundamental level, scientists were previously unaware of its role in natural killer cell function. With colleagues Priyanka Sathe and Rebecca Delconte, Dr Huntington established its role.

That knowledge will prove useful for the development of new drugs to treat cancers.

Potential benefits include reduced side effects from treatment, as the killer cells only target foreign, diseased or cancerous cells, unlike chemotherapy which targets healthy cells as well.

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Scientists discover killer cells' ''on switch''

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Newswise Hematopoietic stem cells (HSCs) give rise to all other blood cell types, but their development and how their fate is determined has long remained a mystery. In a paper published online this week in Nature, researchers at the University of California, San Diego School of Medicine elaborate upon a crucial signaling pathway and the role of key proteins, which may help clear the way to generate HSCs from human pluripotent precursors, similar to advances with other kinds of tissue stem cells.

Principal investigator David Traver, PhD, professor in the Department of Cellular and Molecular Medicine, and colleagues focused on the Notch signaling pathway, a system found in all animals and known to be critical to the generation of HSCs in vertebrates. Notch signaling between emitting and receiving cells is key to establishing HSC fate during development, said Traver. What has not been known is where, when and how Notch signal transduction is mediated.

Traver and colleagues discovered that the Notch signal is transduced into HSC precursor cells from signal emitting cells in the somite embryologic tissues that eventually contribute to development of major body structures, such as skeleton, muscle and connective tissues much earlier in the process than previously anticipated.

More specifically, they found that JAM proteins, best known for helping maintain tight junctions between endothelial cells to prevent vascular leakage, were key mediators of Notch signaling. When the researchers caused loss of function in JAM proteins in a zebrafish model, Notch signaling and HSCs were also lost. When they enforced Notch signaling through other means, HSC development was rescued.

To date, it has not been possible to generate HSCs de novo from human pluripotent precursors, like induced pluripotent stem cells, said Traver. This has been due in part to a lack of understanding of the complete set of factors that the embryo uses to make HSCs in vivo. It has also likely been due to not knowing in what order each required factor is needed.

Our studies demonstrate that Notch signaling is required much earlier than previously thought. In fact, it may be one of the earliest determinants of HSC fate. This finding strongly suggests that in vitro approaches to instruct HSC fate from induced pluripotent stem cells must focus on the Notch pathway at early time-points in the process. Our findings have also shown that JAM proteins serve as a sort of co-receptor for Notch signaling in that they are required to maintain close contact between signal-emitting and signal-receiving cells to permit strong activation of Notch in the precursors of HSCs.

The findings may have far-reaching implications for eventual development of hematopoietic stem cell-based therapies for diseases like leukemia and congenital blood disorders. Currently, it is not possible to create HSCs from differentiation of embryonic stem cells or induced pluripotent stem cells pluripotent cells artificially derived from non-pluripotent cells, such as skin cells that are being used in other therapeutic research efforts.

Co-authors include Isao Kobayashi, Jingjing Kobayashi-Sun, Albert D. Kim and Claire Pouget, UC San Diego Department of Cellular and Molecular Medicine; Naonobu Fujita, UC San Diego Section of Cell and Developmental Biology; and Toshio Suda, Keio University, Japan.

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New Blood: Tracing the Beginnings of Hematopoietic Stem Cells

Aug 13, 2014 Growing stem cells in conditions free of animal material makes them safe for use in humans. Credit: Eraxion/iStock/Thinkstock

Human stem cells produced through genetic reprogramming are beset by safety concerns because current techniques alter the DNA of the stem cells and use material from animals to grow them. Now, A*STAR researchers have developed an efficient approach that produces safe, patient-specific human stem cells.

Human induced pluripotent stem cells have the potential to treat a number of diseases without the ethical issues associated with embryonic stem cells. Pluripotent stem cells can be produced from adult cells by introducing genes that reprogram them. Typically, the stem cells are grown on a layer of mouse cells in solutions (known as media) that contain animal proteinsand therefore, potentially may also carry disease. For such stem cells to be safe for use in humans, they need to be grown in 'xeno-free' conditions, which are devoid of material from other animals.

Andrew Wan and Hong Fang Lu at the A*STAR Institute of Bioengineering and Nanotechnology in Singapore and colleagues set out to develop a new xeno-free system. The researchers carried out the genetic reprogramming of cells on an artificially produced protein substrate rather than mouse cells. They also used media that contained no animal components. The result was more efficient reprogramming than seen with conventional approaches.

"A xeno-free system will eliminate the risk of disease transmission from other species, which is important for regulatory approval," explains Wan. "Yet there have been few studies on cell reprogramming under totally xeno-free conditions."

The researchers went one step further by addressing the problem of cells acquiring alterations to their DNA during reprogramming.

"Incorporation of transgenes into the genome of the cell poses another safety issue, risking unwanted genetic alterations," explains Lu. "In our work, the transgenes were introduced to initiate the reprogramming, but after this they were removed from the cell, leading to transgene-free stem cells."

The researchers demonstrated that after genetic reprogramming and the removal of the added genes, the stem cells could still develop into different cells types. They were even able to induce them to form dopaminergic neurons, the type that degenerates in Parkinson's disease. The conditions in which the stem cells were grown mean that they are suitable for clinical use and can be derived from a patient's own cells, ensuring complete compatibility.

"Regulatory approval for clinical application of stem cells largely depends on the conditions in which the stem cells are derived," says Wan. "We present a workable protocol for the reprogramming of fibroblasts to stem cells that minimizes any potential safety risks."

Explore further: Discovery may make it easier to develop life-saving stem cells

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Animal-free reprogramming of adult cells improves safety

TO SOME people, the term stem cell may seem kind of taboo. I personally would not want something from animals injected into my system. But Im okay with non-invasive treatments, so I was interested to try out a plant-based stem cell facial.

After cleansing and toning, cotton pads moistened with a clear solution were laid on my eyelids to protect them from a three-minute steaming session. This was followed by a special tool called a scrubber that kind of looks like a computer mouse, but helps to remove dead skin cells and unblock pores without using the rather painful pricking tool.

Next, a rejuvenating gel was applied, followed by the plant-derived stem cell formula. A unique cooling machine was used to massage it into the skin for 10 minutes. Using this machine for cold electrophoresis helps the skin absorb serums and vitamins, without having to use injections. This was great for someone like me, who is wary of invasive treatments. The cooling machine feels like having an ice-cold metal ball massaged on the face; very invigorating, indeed.

Just when I thought my skin already got a lot of pampering, the stem cell was followed by a face mask full of natural vitamins. While it penetrated into my skin, I was given an arm and foot massage, which was nice for further relaxation.

With my combination skin, I looked pretty greasy right afterwards. When I woke up the next day, I didnt see a visible difference in my skin, but it was very smooth and supple to the touch. You may not see instant results with a treatment like this, but its a good treatment to maintain radiance, softness and hydration from beneath the surface of the skin.

This type of facial is not recommended for those with oily or acne-prone skin because the added oiliness may exacerbate problems, but it is ideal for those with dry or mature skin, as it is deeply nourishing and moisturizing. After the first treatment or over time, depending on the condition of your skin, stem cell diminishes fine lines, prevents wrinkles, and promotes cell renewal (a process that slows with age) to give that glowing look that signifies healthy, youthful skin.

I tried out the stem cell facial at Lohas skin and slimming center on Paseo Saturnino, Banilad. Its a more upscale experience here with your own room, as opposed to being in one large room with dividers, in case privacy is an issue for you. All of their machines and products are brought in from Korea and their staff, like my therapist Jennylyn, are highly knowledgeable and know just how much pressure to apply during the treatment. The service, facilities and products used add up to a luxurious treatment session that makes one feel very pampered.

Published in the Sun.Star Cebu newspaper on August 15, 2014.

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Trying out a stem cell facial

A cure for a range of blood disorders and immune diseases is in sight, according to scientists who have unravelled the mystery of stem cell generation.

The Australian study, led by researchers at the Australian Regenerative Medicine Institute (ARMI) at Monash University and the Garvan Institute of Medical Research, is published today in Nature. It identifies for the first time mechanisms in the body that trigger hematopoietic stem cell (HSC) production.

Found in the bone marrow and in umbilical cord blood, HSCs are critically important because they can replenish the body's supply of blood cells. Leukemia patients have been successfully treated using HSC transplants, but medical experts believe blood stem cells have the potential to be used more widely.

Lead researcher Professor Peter Currie, from ARMI explained that understanding how HSCs self-renew to replenish blood cells is a "Holy Grail" of stem cell biology.

"HSCs are one of the best therapeutic tools at our disposal because they can make any blood cell in the body. Potentially we could use these cells in many more ways than current transplantation strategies to treat serious blood disorders and diseases, but only if we can figure out how they are generated in the first place. Our study brings this possibility a step closer," he said.

A key stumbling block to using HSCs more widely has been an inability to produce them in the laboratory setting. The reason for this, suggested from previous research, is that a molecular 'switch' may also be necessary for HSC formation, though the mechanism responsible has remained a mystery, until now.

In this latest study, ARMI researchers observed cells in the developing zebra fish -- a tropical freshwater fish known for its regenerative abilities and optically clear embryos -- to gather new information on the signalling process responsible for HSC generation.

Using high-resolution microscopy researchers made a film of how these stem cells form inside the embryo, which captured the process of their formation in dramatic detail.

Professor Currie said when playing back these films they noticed that HSCs require a "buddy" cell type to help them form. These "buddies," known as endotome cells, have stem cell inducing properties,

"Endotome cells act like a comfy sofa for pre HSCs to snuggle into, helping them progress to become fully fledged stem cells. Not only did we identify some of the cells and signals required for HSC formation, we also pinpointed the genes required for endotome formation in the first place," Professor Currie said.

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Cell discovery brings blood disorder cure closer

Australian scientists studying zebrafish have stumbled upon what they say is one of the most significant discoveries in stem cell research.

In research published on Thursday in the journal Nature, the Monash University scientists revealed that they uncovered how one of the most important stem cells in blood and bone marrow, the haematopoietic stem cell (HSC), is formed.

Professor Peter Currie, from Monash University's Australian Regenerative Medicine Institute, said the discovery brought researchers closer to growing HSCs in a lab.

"HSCs are the basis of bone marrow transplantations as a therapy, so when a leukaemia patient receives bone marrow, it's really these HSCs that do the heavy lifting," Professor Currie said.

"So when clinicians do bone marrow transplants, they need to find a matching donor recipients and we know that's a hit-or-miss procedure.

"So for many years people have been trying to make HSCs in the dish, and they've had very little success in doing this."

Professor Currie, who led the study, said the discovery brought scientists much closer to achieving that aim.

"It's the discovery of a completely new cell type that basically is required to give instructions to the HSC to make it become what it needs to become," he said.

"It means we now understand how HSC form in the body better, we can use that information to try to grow these cells in the dish and we hope that will lead to better treatment for people with leukaemia and blood disorders."

Professor Currie said he specialises in muscle stem cell biology and accidentally came across the discovery while studying muscle stem cells in zebrafish.

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Stem cell discovery: Australian scientists make significant find while studying zebrafish