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Category Archives: California Stem Cells

Stem cells, Darth Vader and the high cost of hope and hype …

Posted: June 1, 2015 at 11:44 pm

Darth Vader: Photo by Stefano Buttafoco

Its not very often that you get stories about stem cells that mention Darth Vader, Obi Wan Kenobi, the Pittsburgh Steelers and a Beverly Hills plastic surgeon, but those references all popped up in a recent flurry of articles that are shining yet again the light on many of the unproven, unregulated uses of stem cells to treat everything from arthritis to Parkinsons disease.

Lets start with an article by Associated Press (AP) writer Will Graves who digs into the use of stem cells in sports. Graves does a good job of highlighting all the reasons why an athlete would try a stem cell therapy quoting Dr. Jim Bradley, a team physician with the Steelers:

They want the cutting edge, anything that is cutting edge that can get their guys a couple more years in the league. If I was an agent, Id want the same thing.

But Graves also does a fine job of pointing out that these therapies are unproven, and that in many cases athletes go overseas to get them because those clinics do not have to meet the same strict regulations as clinics here in the US.

Traveling to a place like the Caymans, thats like saying Im going to Mexico to have an appendectomy to save $80,' said Dr. Matthew Matava, head physician for the St. Louis Rams and the NHLs St. Louis Blues. It looks like its not very smart or youre grasping at straws.

He also quotes Dr. Freddie Fu, head physician for the University of Pittsburgh athletics program, saying there is far too much uncertainty to take risks. Fu says in many cases the people delivering the therapies dont even know where these stem cells might go, or what they might do:

You can have one cell be Obi Wan Kenobi, the other is Darth Vader. Youre not sure which way its going to go.

Matthew Perrone starts his piece in the Huffington Post, with a paragraph that is both gripping and disgusting:

The liquid is dark red, a mixture of fat and blood, and Dr. Mark Berman pumps it out of the patients backside. He treats it with a chemical, runs it through a processor and injects it into the womans aching knees and elbows.

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UCSDs Stem Cell Break Through Could Lead to Treatment for Type-1 Diabetes

Posted: April 3, 2015 at 7:59 pm

A UC San Diego student examines a bacteria culture. Photo courtesy UCSD

Researchers at the UC San Diego School of Medicine announced Thursdaytheyve discovered why its so hard to use stem cells to make liver and pancreatic cells, and their findings could lead to new treatments for diseases such astype-1 diabetes.

It turns out that the chromosomes in laboratory stem cells open slowly over time, in the same sequence that occurs during embryonic development. It isnt until certain chromosomal regions have reached the open state that they are able to respond to added growth factors and become liver or pancreatic cells, the researchers said.

Our ability to generate liver and pancreatic cells from stem cells has fallen behind the advances weve made for other cell types, said Dr. Maike Sander, a professor of pediatrics and cellular and molecular medicine, and director of the Pediatric Diabetes Research Center at UCSD.

So we havent yet been able to do things like test new drugs on stem cell-derived liver and pancreatic cells, Sander said. What we have learned is that if we want to make specific cells from stem cells, we need ways to predict how those cells and their chromosomes will respond to the growth factors.

Researchers have focused on stem cells for treating disease because they can be altered into hundreds of types of cells.

According to UCSD, it sometimes takes up to seven carefully orchestrated steps of adding certain growth factors at specific times to coax stem cells into the desired cell type.

Sander said the study found that the chromosomal regions that need to open before a stem cell can fully differentiate are linked to regions where there are variations in certain disease states. That means if a genetic variation in someones chromosomal region doesnt open at the right time, they could be more susceptible to a disease affecting that cell type.

Herteam is now working to further investigate what role, if any, the chromosomal regions and their variations play in diabetes.

Researchers with the University of Pennsylvania, Penn State University and Ludwig Institute for Cancer Research assisted with the study, funded by the National Institutes of Health, California Institute for Regenerative Medicine, the Helmsley Charitable Trust and Juvenile Diabetes Research Foundation.

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New UC San Diego Findings Could Lead To Diabetes Treatment

Posted: April 3, 2015 at 7:59 pm

Researchers at the UC San Diego School of Medicine announced today they've discovered why it's so hard to use stem cells to make liver and pancreatic cells, and their findings could lead to new treatments for diseases like type 1 diabetes.

It turns out that the chromosomes in laboratory stem cells open slowly over time, in the same sequence that occurs during embryonic development. It isn't until certain chromosomal regions have reached the open state that they are able to respond to added growth factors and become liver or pancreatic cells, the researchers said.

"Our ability to generate liver and pancreatic cells from stem cells has fallen behind the advances we've made for other cell types," said Dr. Maike Sander, a professor of pediatrics and cellular and molecular medicine, and director of the Pediatric Diabetes Research Center at UCSD.

"So we haven't yet been able to do things like test new drugs on stem cell-derived liver and pancreatic cells," Sander said. "What we have learned is that if we want to make specific cells from stem cells, we need ways to predict how those cells and their chromosomes will respond to the growth factors."

Researchers have focused on stem cells for treating disease because they can be altered into hundreds of types of cells.

According to UCSD, it sometimes takes up to seven carefully orchestrated steps of adding certain growth factors at specific times to coax stem cells into the desired cell type.

Sander said the study found that the chromosomal regions that need to open before a stem cell can fully differentiate are linked to regions where there are variations in certain disease states. That means if a genetic variation in someone's chromosomal region doesn't open at the right time, they could be more susceptible to a disease affecting that cell type.

His team is now working to further investigate what role, if any, the chromosomal regions and their variations play in diabetes.

Researchers with the University of Pennsylvania, Penn State University and Ludwig Institute for Cancer Research assisted with the study, funded by the National Institutes of Health, California Institute for Regenerative Medicine, the Helmsley Charitable Trust and Juvenile Diabetes Research Foundation.

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New UC San Diego Findings Could Lead To Diabetes Treatment

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Stem Cell Center – University of California, Riverside

Posted: March 18, 2015 at 2:53 am

Stem cells are fast becoming relevant to all aspects of our society, with medical, scientific, ethical, political, and economic implications. Therefore it is important that scientists and non-scientists alike be provided with accurate information about stem cell biology. The goals of the UCR Stem Cell Center is to provide the members of the community with a better understanding of the science of stem cells so that they have the necessary tools to make reasoned decisions about the related society issues.

UCR has a strong history in training undergraduate and graduate students and is developing a complete training program in stem cell biology.

Stem cell biology is currently one of the most exciting fields in science with the potential not only to answer basic biological questions but also to provide new therapies and treatments for debilitating diseases. Some of the most important biomedical breakthroughs of this century are likely to come through the use of stem cell technology.

Diseases that could in the future be treated by stem cell biology include (but are not limited to) diabetes, Parkinsons disease, spinal cord injury, Alzheimers disease, aging, heart disease, stroke, burns, amputations, and osteoarthritis.

Stem cell biology will form an important component in both the UCR Health Sciences Research Institute and future Medical School, which will work to facilitate translational research.

Web link to UCR Health Sciences Research Initiative: http://www.hsri.ucr.edu/ Web link to Medical School: http://www.medschool.ucr.edu/

Basic research is needed to understand, control, and use stem cells safely and effectively for therapeutic and environmental purposes.

The UCR Stem Cell Center is making major contributions to stem cell biology by attacking basic biological problems at an interdisciplinary level, enabling translation to the clinical level, and by using stem cells to monitor the effects of the environment on human health.

The Center has faculty working with various types of stem cells including human embryonic, mouse embryonic, hematopoietic, and human umbilical cord stem cells.

Stem cells are valuable tools that have the potential not only to treat numerous diseases, but also to study development and evaluate the toxicity of chemicals and drugs.

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Heart-on-a-chip beats a steady rhythm

Posted: March 12, 2015 at 7:53 am

The growing number of biological structures being grown on chips in various laboratories around the world is rapidly replicating the entire gamut of major human organs. Now one of the most important of all a viable functioning heart has been added to that list by researchers at the University of California at Berkeley (UC Berkeley) who have taken adult stem cells and grown a lattice of pulsing human heart tissue on a silicon device.

Sourced from human-induced pluripotent stem cells able to be persuaded into forming many different types of tissue, the human heart device cells are not simply separate groups of cells existing in a petri dish, but a connected series of living cells molded into a structure that is able to beat and react just like the real thing.

"This system is not a simple cell culture where tissue is being bathed in a static bath of liquid," said study lead author Anurag Mathur, a postdoctoral researcher at UC Berkeley. "We designed this system so that it is dynamic; it replicates how tissue in our bodies actually gets exposed to nutrients and drugs."

Touted as a possible replacement for living animal hearts in drug-safety screening, the ability to easily access and rapidly analyze a heart equivalent in experiments presents appealing advantages.

"Ultimately, these chips could replace the use of animals to screen drugs for safety and efficacy," said professor of bioengineering at UC Berkeley, and leader of the research team, Kevin Healy.

The cardiac microphysiological system, as the team calls its heart-on-a-chip, has been designed so that its silicon support structure is equivalent to the arrangement and positioning of conjoining tissue filaments in a human heart. To this supporting arrangement, the researchers loaded the engineered human heart cells into the priming tube, whose cone-shaped funnel assisted in aligning the cells in a number of layers and in one direction.

In this setup, the team created microfluidic channels on each side of the cell holding region to replicate blood vessels to imitate the interchange of nutrients and drugs by diffusion in human tissue. The researchers believe that this arrangement may also one day provide the ability to view and gauge the expulsion of metabolic waste from the cells in future experiments.

"Many cardiovascular drugs target those channels, so these differences often result in inefficient and costly experiments that do not provide accurate answers about the toxicity of a drug in humans," said Professor Healy. "It takes about US$5 billion on average to develop a drug, and 60 percent of that figure comes from upfront costs in the research and development phase. Using a well-designed model of a human organ could significantly cut the cost and time of bringing a new drug to market."

The use of animal organs to forecast human reactions to new drugs is problematic, the UC Berkeley researchers note, citing the fundamental differences between species as being responsible for high failure rates in using these models. One aspect responsible for this failure is to be found in the difference in the ion channel structure between human and other animals where heart cells conduct electrical currents at different rates and intensities. It is the standardized nature of using actual human heart cells that the team sees as the heart-on-a-chip's distinct advantage over animal models.

The UC Berkeley device is certainly not the first replication of an organ-on-a-chip, but potentially one of the first successful ones to integrate living cells and artificial structures in a single functioning unit. Harvard's spleen-on-a-chip, for example, replicates the operation of the spleen, but does so by using a set of circulatory tubes containing magnetic nanobeads.

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Heart-on-a-chip beats a steady rhythm

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Bioengineers put human hearts on a chip to aid drug screening

Posted: March 10, 2015 at 2:50 am

VIDEO:Shown is human heart tissue, derived from adult stem cells, before and after exposure to isoproterenol, a drug used to treat bradycardia (slow heart rate) and other heart problems. The... view more

Credit: Video by Dr. Anurag Mathur/Healy Lab

Berkeley -- When University of California, Berkeley, bioengineers say they are holding their hearts in the palms of their hands, they are not talking about emotional vulnerability.

Instead, the research team led by bioengineering professor Kevin Healy is presenting a network of pulsating cardiac muscle cells housed in an inch-long silicone device that effectively models human heart tissue, and they have demonstrated the viability of this system as a drug-screening tool by testing it with cardiovascular medications.

This organ-on-a-chip, reported in a study to be published Monday, March 9, in the journal Scientific Reports, represents a major step forward in the development of accurate, faster methods of testing for drug toxicity. The project is funded through the Tissue Chip for Drug Screening Initiative, an interagency collaboration launched by the National Institutes of Health to develop 3-D human tissue chips that model the structure and function of human organs.

"Ultimately, these chips could replace the use of animals to screen drugs for safety and efficacy," said Healy.

The study authors noted a high failure rate associated with the use of nonhuman animal models to predict human reactions to new drugs. Much of this is due to fundamental differences in biology between species, the researchers explained. For instance, the ion channels through which heart cells conduct electrical currents can vary in both number and type between humans and other animals.

"Many cardiovascular drugs target those channels, so these differences often result in inefficient and costly experiments that do not provide accurate answers about the toxicity of a drug in humans," said Healy. "It takes about $5 billion on average to develop a drug, and 60 percent of that figure comes from upfront costs in the research and development phase. Using a well-designed model of a human organ could significantly cut the cost and time of bringing a new drug to market."

The heart cells were derived from human-induced pluripotent stem cells, the adult stem cells that can be coaxed to become many different types of tissue.

The researchers designed their cardiac microphysiological system, or heart-on-a-chip, so that its 3-D structure would be comparable to the geometry and spacing of connective tissue fiber in a human heart. They added the differentiated human heart cells into the loading area, a process that Healy likened to passengers boarding a subway train at rush hour. The system's confined geometry helps align the cells in multiple layers and in a single direction.

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Gordie Howes Son Says Dads Recovery No Fluke, Excited For Future Of Stem Cell Treatment

Posted: March 8, 2015 at 10:51 pm

By Ashley Dunkak @AshleyDunkak

CBS DETROIT Murray Howe, the head of the radiology department at ProMedica Toledo Hospital, understands the skepticism of those who question the stem cell treatment his father Gordie, also known as Mr. Hockey, received in December in Tijuana, Mexico.

Gordies health had been slowly declining even before the stroke he suffered in late October, and he was essentially bedridden when Murray and his brother Marty took him to Mexico to participate in a clinical trial. They did not have high hopes he was so far gone, Murray recalled but after each step of the two-part process, Gordie improved rapidly, once again able to walk and talk, repossessed of his wit and humor. Murray and his siblings were floored. So were the therapists who had been working with Gordie after his stroke.

Some physicians have scoffed at the idea of stem cells helping an individual who has had a stroke, but Murray a doctor himself says his fathers recovery after treatment opened his eyes to stem cells as a potential game-changer.

Speaking as a medical professional, its so frustrating when you cant really do anything for a patient, said Howe, the head of the radiology department at Toledo Hospital. You give them kind of a death sentence and you say, Well thats all you get. Theres nothing we can really offer. Its so sad. So now to be able to have on the brink of some huge hope for these patients is really, really exciting. As a medical professional, to me, theres never been anything more exciting in my entire career than this.

Murray does not blame people for being skeptical, and he agrees more research on the capabilities of stem cells is needed to show definitively what they can do. To say Murray is optimistic, however, would be a serious understatement.

Theres quite a few individuals out there who are calling themselves stem cell experts or this or that, kind of saying that theres no data to support that stem cells work on ischemic strokes, but thats really not true at all, Murray said. Theres at least 50 clinical studies that are going on across the world that are demonstrating its safety and working on demonstrating its efficacy, and the preliminary results on the ones that Ive seen are tremendous, so the data is clearly there. I think that people across the world in the next couple years are going to be as blown away as I was with our father when they see the power of stem cells and what they do for patients with not just stroke but with dementia and traumatic brain injuries and spinal cord injuries.

My dads case is by no means the only one, Murray continued. Hes kind of like in the middle. Theres examples of patients that have had a far greater result. Im so thrilled for my dad, but by no means was my dad a fluke or a random event. The studies are ongoing, and I think the point of any of the, I guess, naysayers is that Gordie Howe may be anecdotal and we need more research, and I totally agree with that. In fact, based on what weve seen with my father, I would say that we as a country and as a world should make a concerted effort to put as much time and energy as we can into investigating the power of stem cells because I really think that based on what Im seeing this is going to be a game-changer for medicine and a game-changer for quality of life for so many people that have non-option diseases like stroke or dementia.

Heading to Tijuana for treatment was a last-ditch effort to save Gordie, but it was not one the family undertook on a whim, Murray said.

Im well aware of hucksters and con games and this type of thing, and our family has never been about traveling the world to find the miracle cure, Murray said. Im a very mainstream physician. Ive always relied heavily on data and on long-term studies to prove the safety and efficacy of any treatment. For our father, we just our goal has always just been quality of life and comfort. When my mom was sick with her dementia that was our only priority was just keep her comfortable, keep her healthy, as healthy as possible, and keep her safe, and that was it. We had a number of people contact us saying, You know, we could help your mom with this pill and that pill, and I looked at everything that anybody presented to us, but to me there was nothing that showed any data that would made me want to experiment, if you will, with my mom.

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Culture Clash: How Stem Cells Are Grown Affects Their Genetic Stability

Posted: February 26, 2015 at 12:51 am

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Newswise The therapeutic promise of human stem cells is indisputably huge, but the process of translating their potential into effective, real-world treatments involves deciphering and resolving a host of daunting complexities.

Writing in the February 25 online issue of the journal PLOS ONE, researchers at University of California, San Diego School of Medicine, with collaborators from The Scripps Research Institute (TSRI), have definitively shown for the first time that the culture conditions in which stem cells are grown and mass-produced can affect their genetic stability.

Since genetic and epigenetic instability are associated with cancers, we worry that similar alterations in stem cells may affect their safety in therapeutic transplants. Certain mutations might make transplanted stem cells more likely to form tumors, introducing the risk of cancer where it didnt exist before, said co-corresponding author Louise Laurent, MD, PhD, assistant professor and director of perinatal research in the Department of Reproductive Medicine at UC San Diego School of Medicine.

This study shows the importance of quality control, added Jeanne F. Loring, PhD, professor and director of the Center for Regenerative Medicine at TSRI, and adjunct professor in the UC San Diego Department of Reproductive Medicine and the studys other co-corresponding author. Its almost certain these cells are safe, but we want to make sure they are free from any abnormalities.

To exploit the transformative powers of human pluripotent stem cells, which include embryonic stem cells and induced pluripotent stem cells, requires producing them in large numbers for transplantation into patients.

During this culturing process, mutations can occur, and mutations that increase cell survival or proliferation may be favored, such that the cells carrying such mutations could take over the culture, said Laurent.

Human pluripotent stem cells are cultured in several different ways. Key variables are the surfaces upon which the cells are cultured, called the substrate, and the methods used to transfer cells from one culture dish into another as they grow, called the passage method.

Originally, scientists determined that stem cells grew best when cultured atop of a feeder layer that included other types of cells, such as irradiated mouse embryonic fibroblasts. For reasons not fully understood, these cells provide stem cells with factors that support their growth. However, concerns about the feeder cells also introducing undesirable materials into stem cells has prompted development of feeder-free cultures.

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Culture Clash: How Stem Cells Are Grown Affects Their Genetic Stability

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CIRM's Klein proposes $100B biomed program

Posted: February 23, 2015 at 2:52 pm

Bob Klein describes his vision of how to increase biomedical funding to hasten discovery and commercialization of disease treatments. He spoke Thursday, Feb. 19, at the annual UCSD Moores Cancer Center symposium.

Bob Klein, the main backer of California's 2004 stem cell initiative has proposed a $100 billion international bond program in life sciences, to speed up research and clinical testing of disease therapies. The program would be focused on stem cells and genomics.

The United States and a few other countries would jump-start the program, and other countries would join, said Klein, a real estate investor, at last Thursday's UCSD Moores Cancer Center symposium.

Klein likened the participation to that already taking place in the stem cell cell program, the California Institute for Regenerative Medicine, created by the 2004 initiative, Proposition 71. CIRM has partnered with 14 other countries to co-fund international research projects. Foreign partners fund scientists in their own countries, while CIRM funds California-based scientists. Klein was CIRM's first chairman. Although he left the agency's governing board in 2011, he remains involved in advancing the agency's objectives.

This partnership leverages funding to create a much greater total impact, Klein said in an on-stage interview with Rep Scott Peters, D-San Diego. Peters, one of the post prominent supporters of federal biomedical funding in Congress, represents much of San Diego's biotech heartland of La Jolla and Sorrento Valley. Beside the financing issues, they also discussed ways to increase political support for biomedical research.

Klein, a real estate developer, drew from his knowledge of crafting bonds to describing how the program would work. The bond program would be seeded by a much smaller amount of seed funding through government-supported agencies, creating leverage.

"Just to give you (an idea) of the multiple effect of bringing critical funds upfront in the process, $100 million (a year) in bonds at the World Bank borrowing rate creates about $2.5 billion in bonds that are supported," Klein said. "At a time of scarce resources for Congress, if they would appropriate on a long term commitment to support international bonds, we could really leverage up to maybe a $100 billion program."

Under that program, each participating country would be allocated an amount of upfront financing to pay.

"Because the borrowing is so much cheaper than anything a country can do, from the surplus funds we raise, which are about 35 percent to 40 percent more than most countries can raise from the same amount of money, we can have an international pool, where we can collaborate and compete through peer review," Klein said.

Klein pointed to the International Finance Facility for Immunization as an international public-private partnership as a financial model. Using long-term government pledges as collateral, the agency can raise capital as needed from the bond markets.

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UCSD scientists awarded $2.7M grants for stem cell research

Posted: February 3, 2015 at 3:59 am

LA JOLLA (CNS) - Two scientists with UC San Diego were awarded a combined $2.7 million in grants from the California Institute for Regenerative Medicine to pursue their studies on stem cell therapies, the school announced Monday.

Shyni Varghese, an associate professor in the Department of Bioengineering and director of the Bio-Inspired Materials and Stem Cell Engineering Laboratory, received a $1.4 CIRM grant to improve the function of transplanted stem cells.

Shaochen Chen, a professor in the Department of Nanoengineering in the Jacobs School of Engineering and a member of UCSD's Institute of Engineering in Medicine, received $1.3 million to develop three-diminensional bioprinting techniques that use heart muscle cells derived from human embryonic stem cells to create new cardiac tissue.

The awards were part of almost $30 million in grants announced at CIRM's monthly meeting in San Francisco, according to UCSD.

"Sometimes even the most promising therapy can be derailed by a tiny problem," said Jonathan Thomas, chairman of the CIRM Board of Directors. "These awards are designed to help find ways to overcome those problems, to bridge the gaps in our knowledge and ensure that the best research is able to keep progressing and move out of the lab and into clinical trials in patients."

Varghese's lab focuses on the interactions of cells with their surrounding micro-environment, and how the conditions necessary to promote normal, healthy survival and growth occur, according to UCSD.

Chen's studies focus on using stem cells to create new heart tissue that would help patients when transplants aren't immediately available.

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