Category Archives: Stem Cell Videos

CHICAGO--(BUSINESS WIRE)--

OncoMed Pharmaceuticals, Inc., a privately held, clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor initiating cells, today highlighted new data presented this afternoon in a poster discussion session at the Annual Meeting of the American Society for Clinical Oncology (ASCO) in Chicago, IL. This represents the first clinical presentation of OMP-59R5, a monoclonal antibody targeting the Notch2 and Notch3 receptors. Authors of the poster, A First-in-Human Phase I Study to Evaluate the Fully Human Monoclonal Antibody OMP-59R5 (anti-Notch2/3) Administered Intravenously to Patients with Advanced Solid Tumors, concluded that OMP-59R5 was generally well tolerated and established maximum tolerated doses (MTDs) of 2.5mg/kg weekly (QW) and 5mg/kg every other week (QoW) for the drug.

The study results were presented by Dr. Anthony Tolcher of The START Center for Cancer Care, San Antonio, TX. Dr. Tolcher noted that the main treatment-related adverse event was diarrhea and there was evidence of Notch pathway modulation with this drug. Dr. David Smith and colleagues at the University of Michigan Cancer Center at Ann Arbor, MI also participated in the Phase I study. The anti-Notch2/3 program is part of OncoMeds collaboration with GlaxoSmithKline.

The Phase I dose-escalation study (3+3 design) was initiated in patients with advanced solid tumors. The investigational antibody, OMP-59R5, was administered to study safety, pharmacokinetics (PK), pharmacodynamics (PD), preliminary efficacy, and to determine the MTD. Thirty patients have been enrolled in four dose-escalation cohorts at doses of 0.5, 1, 2.5, and 5mg/kg administered weekly, as well as two dose-escalation cohorts of 5 and 10mg/kg administered every other week. The study is ongoing and will test an every-three-week dosing schedule.

The most frequently reported drug-related adverse events were: mild to moderate diarrhea, fatigue, nausea, vomiting, decreased appetite, and constipation. Diarrhea was dose related and occurred at doses 2.5mg/kg weekly and appeared less pronounced with every-other-week dosing. The PK of OMP-59R5 was characterized by rapid, dose-dependent clearance. Several patients had prolonged stable disease for 56 days (tumor types included Kaposis Sarcoma, adenoid cystic carcinoma, rectal cancer, and liposarcoma). PD modulation of Notch pathway was detectable in surrogate tissue and in tumor and occurred at doses 1mg/kg. The OMP-59R5 clinical program is advancing toward PhIb/II development in solid tumor indications.

About Anti-Notch2/3

The Notch pathway plays a central role in embryonic development, the regulation of stem and progenitor cells, and is implicated centrally in many human cancers. OMP-59R5 is a fully human IgG2 monoclonal antibody originally identified by binding to Notch2. It inhibits the signaling of both Notch2 and Notch3 receptors. Mouse xenograft studies using minimally-passaged, patient-derived xenografts have shown that OMP-59R5 impedes tumor growth and eliminates CSCs in many tumor types. OMP-59R5 modulates the expression of stromal genes and genes associated with the function of tumor vascular pericytes. Based on preclinical experiments, we believe that OMP-59R5 is a novel anti-cancer agent that inhibits tumor growth through direct actions on tumor cells, including CSCs, and effects on the stroma and vasculature.

About Cancer Stem Cells

Cancer stem cells, a small, resilient subset of cells found in tumors, have the capacity to self-renew and differentiate, leading to tumor initiation and driving tumor growth, recurrence and metastasis. Also referred to as tumor-initiating cells, these cells were first discovered by OncoMeds scientific founders in breast cancer and have subsequently been identified in many other tumor types, including brain, colon, lung, prostate, and pancreatic cancer. Cancer stem cells appear to be preferentially resistant to both standard chemotherapy and radiotherapy. OncoMeds strategy is to improve cancer treatment by specifically targeting the key biologic pathways that are thought to be critical to the activity and survival of cancer stem cells. OncoMeds antibody therapeutics target cancer stem cell proteins and have the potential to be developed against a range of tumor types.

About OncoMed Pharmaceuticals

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OncoMed Presents First-in-Human Phase I Data on Anti-Notch2/3 Antibody at ASCO

Stem cells provided by San Diego-based Stemedica Cell Technologies Inc. are expected to be used soon in a phase I/II clinical trial for chronic heart failure in Mexico.

Stemedica announced May 29 that its strategic Mexico partner, Grupo Angeles Health Services, has received approval for a single-blind randomized clinical trial from Mexicos FDA equivalent regulatory agency, COFEPRIS.

The trial being conducted at multiple hospital sites throughout Mexico will involve Stemedicas adult allogeneic ischemia tolerant mesenchymal stem cells delivered via intravenous infusion. The trial will involve three safety cohorts at different dosages, followed by a larger group being treated with the maximum safe dosage.

The trial, set to begin on or before July 1 with 60 to 80 patients, is one of only two studies using allogeneic stem cells approved by COFEPRIS. The other study approved in 2010 was a clinical trial for ischemic stroke.

We are pleased that we will be working with the largest and most prestigious private medical institution in Mexico to study Stemedicas product for this indication, said Stemedica CEO Maynard Howe in a statement. If successful, our stem cells may provide a treatment option for the millions of patients, both in Mexico and internationally, who suffer from this condition.

Grupo Angeles, comprised of 24 state-of-the-art hospitals, conducts some 100 clinical trials annually, primarily with major global pharmaceutical and medical device companies.

Stemedica stem cells are also currently being used in a phase I/IIa trial for stroke patients at UC San Diego. The 36-patient clinical trial has been progressing about a year and is moving into its third and final cohort, said Dave McGuigan, vice president of marketing and business development for the company. When patient treatments are completed by the end of September, data will be evaluated to determine whether it moves to a full phase IIb trial to primarily determine efficacy in a larger population of 60 to 80 patients, McGuigan said.

Our next step would be to initiate a phase II clinical trial in multiple sites across the U.S. in 2013, he said.

Founded seven years ago, the privately held Stemedica specialty biopharmaceutical company has about 46 locally based employees in the U.S. and an additional eight staff in Switzerland, South Korea and Singapore.

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Stemedica Takes Part in Mexican Clinical Trial

CLEMSON, S.C. The cells Mike Kents own cells, the donated stem cells now coursing through his stricken brothers body are working just fine. Thats what they tell him. His family and the doctors are careful to shield Mike, just 21 years old, from most of the bad news regarding Matts battle with Hodgkins lymphoma and lately there has been plenty of it. But they always make sure to tell him: Your cells are doing great.

It can mess with your head, being a stem-cell donor to your own brother. If something goes wrong, it is only natural to wonder if it was your fault. Were your cells bad? And Mike Kent, a 2009 Washington Post All-Met selection at West Springfield High, has enough on his plate right now not just Matts three-year fight with cancer, but also his own baseball career at Clemson to be saddled with all that guilt. Clemson opens play in the NCAA regionals at Columbia, S.C., on Friday.

(Family photo) - Mike Kent, right, poses with his brother, Matt, when Mike was a high school senior and a pitcher for the West Springfield, Va, baseball team.

Because now, Matts liver is failing, the veins breaking down from the high doses of chemotherapy and radiation. He floats in and out of consciousness in the intensive-care unit at the University of Maryland Medical Center in Baltimore, unaware of his surroundings.

Ill be honest: Ive asked them, Is he going to survive this? said Susan Kent, Matt and Mikes mother, a look of sheer resolve on her face. Of course, the doctors wont answer.

Such an awkward spot for a mother who had raised two boys on her own. One of them, a college sophomore, is playing out his dream, preparing to pitch in college baseballs national championship tournament, his life spread out before him. The other son, 26 years old and a late-bloomer who was just starting to get his life in order before the diagnosis, is fighting for his life.

How do you handle such a fate? You play up the positives, thats how. You visit Matt in the hospital Matt being the one who taught Mike the game of baseball, in the absence of a father and you tell him, in great detail, about all of Mikes solid outings at Clemson: the scoreless relief appearances, the saves. And you spare him the gory details about the ugly ones the three-run homers, the bases-loaded walks, the losses.

And you give Mike the barest of details about Matts setbacks: There are some complications. Some side effects. But while Mike knows most of the more pertinent information the liver failure, the ICU you emphasize what is important, the thing Mike needs to know: Your cells are doing great.

Throwing extra innings

The injections, the doctors told Mike, would make him feel like he had the flu. The drug, Neupogen, was being given in eight doses, spread over four days to produce and stimulate white blood cells in his body in preparation for the stem cell transplant. One thing he shouldnt try to do, they told him, was play baseball.

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NCAA baseball: Mike Kent of Clemson’s biggest save came away from the diamond

ScienceDaily (May 31, 2012) An immune-system receptor plays an unexpected but crucially important role in keeping stem cells from differentiating and in helping blood cancer cells grow, researchers at UT Southwestern Medical Center report today in the journal Nature.

"Cancer cells grow rapidly in part because they fail to differentiate into mature cells. Drugs that induce differentiation can be used to treat cancers," said Dr. Chengcheng "Alec" Zhang, assistant professor in UT Southwestern's departments of physiology and developmental biology. "Our research identified a protein receptor on cancer cells that inhibits differentiation, and knowing the identity of this protein should facilitate the development of new drugs to treat cancers."

The family of proteins investigated in the study could help open a new field of biology integrating immunology with stem cell and cancer research, he added.

"The receptor we identified turned out to be a protein called a classical immune inhibitory receptor, which is known to maintain stemness of normal adult stem cells and to be important in the development of leukemia," he said.

Stemness refers to the blood stem cells' potential to develop into a range of different kinds of cells as needed, for instance to replenish red blood cells lost to bleeding or to produce more white blood cells to fight off infection. Once stem cells differentiate into adult cells, they cannot go back to being stem cells. Current thinking is that the body has a finite number of stem cells and it is best to avoid depleting them, Dr. Zhang explained.

Prior to this study, no high-affinity receptors had been identified for the family of seven proteins called the human angiopoetic-like proteins. These seven proteins are known to be involved in inflammation, supporting the activity of stem cells, breaking down fats in the blood, and growing new blood vessels to nourish tumors. Because the receptor to which these proteins bind had not been identified, the angiopoetic-like proteins were referred to as "orphans," he said.

The researchers found that the human immune-inhibitory receptor LILRB2 and a corresponding receptor on the surface of mouse cells bind to several of the angiopoetic-like proteins. Further studies, Dr. Zhang said, showed that two of the seven family members bind particularly well to the LILRB2 receptor and that binding exerts an inhibitory effect on the cell, similar to a car's brakes.

In the case of stem cells, inhibition keeps them in their stem state. They retain their potential to mature into all kinds of blood cells as needed but they don't use up their energy differentiating into mature cells. That inhibition helps stem cells maintain their potential to create new stem cells because in addition to differentiation, self-renewal is the cells' other major activity, Dr. Zhang said. He stressed that the inhibition doesn't cause them to create new stem cells but does preserve their potential to do so.

In future research, the scientists hope to find subtle differences between stem cells and leukemia cells that will identify treatments to block the receptors' action only in leukemia.

Other UT Southwestern researchers involved in the study from the departments of physiology and developmental biology include postdoctoral researchers Dr. ChangHao Cui, Dr. Xiaoli Chen, Dr. Chaozheng Zhang, Dr. HoangDinh Huynh, and Dr. Xunlei Kang; senior research associates Robert Silvany and Jiyuan Li; and graduate student Xuan Wan. Researchers from the department of immunology include former technician Alberto Puig Cant and Dr. E. Sally Ward, professor of immunology.

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Mechanism that maintains stem cells readiness identified

Researchers trace the source of recurring blood cancers to a few slowly dividing cancer stem cells.

By Cristina Luiggi | May 31, 2012

Brain cancer stem cellsWellcome Images

Why cancer comes back in some patients after chemotherapy has beaten it into remission has been a matter of debate for oncologists. In a new study published in Blood this week, researchers at The Weizmann Institute of Science in Rehovot, Israel, found that in certain blood cancers, slowly-dividing cancer stem cells that are impervious to the actions of chemotherapywhich commonly target fast-dividing cellsare the source for future recurring cancers.

Led by computational biologist Ehud Shapiro, the researchers reconstructed lineage trees of cells sampled from patients with newly diagnosed leukemia and from patients in which leukemia had returned. They found that in some cases, the source of the recurring cancer cells were not rapidly dividing cancer cells that had dodged chemotherapy, but the slowly-dividing stem cells at the root of the tree.

We know that in many cases, chemotherapy alone is not able to cure leukemia, Shapiro said in a press release. Our results suggest that to completely eliminate it, we must look for a treatment that will not only eliminate the rapidly dividing cells, but also target the cancer stem cells that are resistant to conventional treatment.

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Why Some Cancers Come Back

Public release date: 31-May-2012 [ | E-mail | Share ]

Contact: Deborah Wormser deborah.wormser@utsouthwestern.edu 214-648-3404 UT Southwestern Medical Center

DALLAS May 31, 2012 An immune-system receptor plays an unexpected but crucially important role in keeping stem cells from differentiating and in helping blood cancer cells grow, researchers at UT Southwestern Medical Center report today in the journal Nature.

"Cancer cells grow rapidly in part because they fail to differentiate into mature cells. Drugs that induce differentiation can be used to treat cancers," said Dr. Chengcheng "Alec" Zhang, assistant professor in UT Southwestern's departments of physiology and developmental biology. "Our research identified a protein receptor on cancer cells that induces differentiation, and knowing the identity of this protein should facilitate the development of new drugs to treat cancers."

The family of proteins investigated in the study could help open a new field of biology integrating immunology with stem cell and cancer research, he added.

"The receptor we identified turned out to be a protein called a classical immune inhibitory receptor, which is known to maintain stemness of normal adult stem cells and to be important in the development of leukemia," he said.

Stemness refers to the blood stem cells' potential to develop into a range of different kinds of cells as needed, for instance to replenish red blood cells lost to bleeding or to produce more white blood cells to fight off infection. Once stem cells differentiate into adult cells, they cannot go back to being stem cells. Current thinking is that the body has a finite number of stem cells and it is best to avoid depleting them, Dr. Zhang explained.

Prior to this study, no high-affinity receptors had been identified for the family of seven proteins called the human angiopoetic-like proteins. These seven proteins are known to be involved in inflammation, supporting the activity of stem cells, breaking down fats in the blood, and growing new blood vessels to nourish tumors. Because the receptor to which these proteins bind had not been identified, the angiopoetic-like proteins were referred to as "orphans," he said.

The researchers found that the human immune-inhibitory receptor LILRB2 and a corresponding receptor on the surface of mouse cells bind to several of the angiopoetic-like proteins. Further studies, Dr. Zhang said, showed that two of the seven family members bind particularly well to the LILRB2 receptor and that binding exerts an inhibitory effect on the cell, similar to a car's brakes.

In the case of stem cells, inhibition keeps them in their stem state. They retain their potential to mature into all kinds of blood cells as needed but they don't use up their energy differentiating into mature cells. That inhibition helps stem cells maintain their potential to create new stem cells because in addition to differentiation, self-renewal is the cells' other major activity, Dr. Zhang said. He stressed that the inhibition doesn't cause them to create new stem cells but does preserve their potential to do so.

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Researchers identify mechanism that maintains stem cells readiness

Newswise DALLAS May 31, 2012 An immune-system receptor plays an unexpected but crucially important role in keeping stem cells from differentiating and in helping blood cancer cells grow, researchers at UT Southwestern Medical Center report today in the journal Nature.

Cancer cells grow rapidly in part because they fail to differentiate into mature cells. Drugs that induce differentiation can be used to treat cancers, said Dr. Chengcheng Alec Zhang, assistant professor in UT Southwesterns departments of physiology and developmental biology. Our research identified a protein receptor on cancer cells that inhibits differentiation, and knowing the identity of this protein should facilitate the development of new drugs to treat cancers.

The family of proteins investigated in the study could help open a new field of biology integrating immunology with stem cell and cancer research, he added.

The receptor we identified turned out to be a protein called a classical immune inhibitory receptor, which is known to maintain stemness of normal adult stem cells and to be important in the development of leukemia, he said.

Stemness refers to the blood stem cells potential to develop into a range of different kinds of cells as needed, for instance to replenish red blood cells lost to bleeding or to produce more white blood cells to fight off infection. Once stem cells differentiate into adult cells, they cannot go back to being stem cells. Current thinking is that the body has a finite number of stem cells and it is best to avoid depleting them, Dr. Zhang explained.

Prior to this study, no high-affinity receptors had been identified for the family of seven proteins called the human angiopoetic-like proteins. These seven proteins are known to be involved in inflammation, supporting the activity of stem cells, breaking down fats in the blood, and growing new blood vessels to nourish tumors. Because the receptor to which these proteins bind had not been identified, the angiopoetic-like proteins were referred to as orphans, he said.

The researchers found that the human immune-inhibitory receptor LILRB2 and a corresponding receptor on the surface of mouse cells bind to several of the angiopoetic-like proteins. Further studies, Dr. Zhang said, showed that two of the seven family members bind particularly well to the LILRB2 receptor and that binding exerts an inhibitory effect on the cell, similar to a cars brakes.

In the case of stem cells, inhibition keeps them in their stem state. They retain their potential to mature into all kinds of blood cells as needed but they dont use up their energy differentiating into mature cells. That inhibition helps stem cells maintain their potential to create new stem cells because in addition to differentiation, self-renewal is the cells other major activity, Dr. Zhang said. He stressed that the inhibition doesnt cause them to create new stem cells but does preserve their potential to do so.

In future research, the scientists hope to find subtle differences between stem cells and leukemia cells that will identify treatments to block the receptors action only in leukemia.

Other UT Southwestern researchers involved in the study from the departments of physiology and developmental biology include postdoctoral researchers Dr. ChangHao Cui, Dr. Xiaoli Chen, Dr. Chaozheng Zhang, Dr. HoangDinh Huynh, and Dr. Xunlei Kang; senior research associates Robert Silvany and Jiyuan Li; and graduate student Xuan Wan. Researchers from the department of immunology include former technician Alberto Puig Cant and Dr. E. Sally Ward, professor of immunology.

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Researchers Identify Mechanism That Maintains Stem Cells Readiness, Helps Leukemia Cells Growth

Be cautious with stem cells

EDITOR

The secret of restoring health lies in replacing decrepit cells ravaged by disease with stem cells. This advance in stem cell research follows and is closely linked to the simultaneous announcement by former US President Bill Clinton and British Prime Minister John Major in 2000 that scientists had unravelled the human genome by more than 90 percent. The breakthrough of the Human Genome Project was hailed in superlative terms as advancement in the treatment of cancer and hereditary diseases. Clinton described it as the first survey of the entire human genome and "the most wondrous map ever produced by humankind". A couple of years earlier, physician-geneticist Francis Collins, that leading light noted for his discoveries of disease genes, had described the advance in breaking the human genetic code as something that would be judged by history as "more significant than even splitting the atom or going to the moon".

However, the same sage had warned: "We have a small lantern in the form of a gene, but the lantern doesn't penetrate more than a couple of hundred feet. We don't know whether we're going to encounter chasms, rock walls or mountain ranges along the way." It is this warning that we want to draw attention to. In doing so, we recall that Dolly, the cloned sheep that was eventually euthanised after being diagnosed with progressive lung disease in 2003, was the culmination of embryonic stem cell research that pitted moral scruples against science in yet another of their cyclical rancorous confrontations. In the end, governments ordered a stop to what they feared could degenerate into man playing God. It is important to note that the theatre of this apparent antipathy between metaphysics and science was the citadel of the latter in Western Europe and North America, and not some windswept desert country on a plateau in southern Africa. We feel compelled to issue this warning because countries defined by widespread ignorance have often provided the ideal environment for rogue scientists to conduct their nefarious experiments in pursuit of wicked goals. We say this because while the Ministry of Agriculture (MoA) has perhaps the highest concentration of educated Batswana, they simply looked the other way as controversy around genetically modified foods raged everywhere else in the world.

Our country being a net exporter of food, it was incumbent upon MoA to at least mount a deliberate awareness campaign and insist on adequate labelling of food. But where food production remains an elusive goal, it must be too much to expect MoA to understand that the end aim of food and pharmaceutical multinationals is depletion of botanical resources in the so-called Third Word and dependence on the West. Hence we receive news that enabling legislation for a stem cell facility is to be passed in July with a sense of trepidation.

Today's thought"The world is a dangerous place, not because of those who do evil, but because of those who look on and do nothing."

- Albert Einstein

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Be cautious with stem cells

GRAND RAPIDS, MI -- A stem cell treatment investigated for Huntingtons disease holds out hope that scientists will someday be able to reverse damage caused by the degenerative brain disorder.

The technique, which uses reprogrammed skin cells from a Huntingtons patient, successfully restored motor functions in rats, said Dr. Patrik Brundin, a Van Andel Institute researcher who was involved in the study.

Its an interesting step, one weve been hoping for, he said. Its exciting.

The technique also will be tested in treatments for Parkinsons disease, said Brundin, who came to VAI from Sweden in October to lead the institutes Parkinsons research.

Scientists from Sweden, South Korea and the U.S. collaborated on the study, which was published online Monday in the journal Stem Cells.

Brundin said researchers took stem cells derived from the skin of a patient with Huntingtons disease and converted them to brain cells or nerve cells in culture dishes in the lab. The cells were transplanted into the brains of rats that had an experimental form of Huntingtons, and the rats motor functions improved.

The unique features of the (stem cell approach) means that the transplanted cells will be genetically identical to the patient, Jihwan Song, an associate professor at CHA University in Seoul and co-author of the study, said in a statement released by VAI. Therefore, no medications that dampen the immune system to prevent graft rejection will be needed.

Brundin estimated the research might lead to treatments for humans in five to 10 years, although he acknowledged a timeframe is difficult to predict. Researchers are eager to find a new treatment for Huntingtons because there is nothing really powerful to offer currently, he said.

Huntingtons is a genetic disorder affecting one in every 10,000 Americans that slowly diminishes a persons ability to walk, talk and reason. A child of a parent who has Huntingtons has a 50 percent chance of inheriting the gene that causes it.

Medications can relieve some symptoms in some cases, but there are no treatments available that can slow the disease, according to the Huntingtons Disease Society of America.

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First treatment for Huntington's disease shows promise in rats, Van Andel Institute scientist says

This finding can help researchers model diseases in the lab, and allow these diseases to be studied

Researchers from the University of Wisconsin-Madison have found a way to turn both embryonic and induced pluripotent stem cells into cardiomyocytes.

Sean Palecek, study leader and professor of chemical and biological engineering at the University of Wisconsin-Madison, along with Timothy Kamp, professor of cardiology at UW School of Medicine and Public Health, and Xiaojun Lian, a UW graduate student, have developed a technique for abundant cardiomyocyte production, which will allow scientists to better understand and treat diseases.

Cardiomyocytes are important cells that make up the beating heart. These cells are extremely difficult to obtain, especially in large quantities, because they only survive for a short period of time when retrieved from the human heart.

But now, the UW researchers have found an inexpensive method for developing an abundance of cardiomyocytes in the laboratory. This finding can help researchers model diseases in the lab, and allow these diseases to be studied. Researchers will also be able to tests drugs that could help fight these diseases, such as heart disease.

"Many forms of heart disease are due to the loss or death of functioning cardiomyocytes, so strategies to replace heart cells in the diseased heart continue to be of interest, said Kamp. "For example, in a large heart attack up to 1 billion cardiomyocytes die. The heart has a limited ability to repair itself, so being able to supply large numbers of potentially patient-matched cardiomyocytes could help."

The UW research team found that changing a signaling pathway called Wnt can help guide stem cell differentiation to cardiomyocytes. They just turned the Wnt pathway on and off at different times using two small molecule chemicals.

"Our protocol is more efficient and robust," said Palecek. "We have been able to reliably generate greater than 80 percent cardiomyocytes in the final population while other methods produce about 30 percent cardiomyocytes with high batch-to-batch variability.

"The biggest advantage of our method is that it uses small molecule chemicals to regulate biological signals. It is completely defined, and therefore more reproducible. And the small molecules are much less expensive than protein growth factors."

This study was published in the journal Proceedings of the National Academy of Sciences.

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New Method Turns Embryonic/Induced Pluripotent Stem Cells into Cardiac Muscle Cells