On stem cells, athletics and the world series (Go Giants!)

Today the San Francisco Giants will be celebrating their World Series victory with a parade that will draw hundreds of thousands of fans to AT&T park, directly across the street from CIRM headquarters.

With sports so much on our minds here at CIRM, this seems like a good day to talk about stem cells in athletics. The topic made news recently thanks to a story written by Timothy Caulfield in The Atlantic. Caulfield, who is a professor at the Faculty of Law and School of Public Health, University of Alberta, is a long-time follower of stem cell research, particularly the trend of stem cell tourism where people travel overseas for unproven stem cell injections.

One point I was glad to see him make is the question of what, exactly, is a “stem cell treatment”? It’s a pretty generic term for a wide range possible treatments. A bone marrow transplant is by far the most common stem cell therapy because it replaces a person’s own blood-forming stem cells with donor stem cells that recreate the person’s blood system. This type of stem cell transplant is commonly used to treat blood disorders like leukemia. Other types of stem cell therapies in development involve transplanting neural stem cells to treat brain disorders and transplanting cells derived from embyonic or iPS cells to treat a wide range of diseases. There is no one “stem cell treatment”.

In the case of sports, most so-called stem cell treatments are really just a matter of taking tissue from one part of the body (fat, for example) and injecting it somewhere else (like a shoulder, knee or elbow). Whether or not stem cells are actually involved is unclear. As Caulfield writes:

In fact, it is an open question in the research community whether this work should truly be considered “stem cell” therapy. As noted by colleague Mick Bhatia, Director and Senior Scientist McMaster Stem Cell and Cancer Research Institute, “these injury therapies lack any evidence to indicate ‘stem cells’ by any definition or means are being used. Any therapeutic effects noted are most likely from any cell type being injected, including cell lines, that would cause local anti-inflammatory response that is both transient (days) and does not involve any stem cell biology.” His blunt conclusion: “Lots of stem cell conclusions here are bogus all the way around … The treatment fetches a lot of money by claiming a stem cell therapy is being used.”

He goes on to blame the media for talking up the athlete’s treatments as “stem cell therapies”, suggesting that these stories help market unproven, unregulated clinics overseas. For those who haven’t been following stem cell tourism, we have more information on our website and recently shot this short video with stem cell scientist Larry Goldstein at UCSD:

Despite his concerns about overblown claims among athletes, Caulfield says he’s optimistic about the field of stem cell research.

To be clear, there is great promise in this area. I firmly believe that stem cell treatments will, one day, help athletes, both professional and recreational, recover from injury. Indeed, there are teams of researchers all over the world, some funded by the NFL, working on this right now. But we aren’t there yet.

It’s good to see Peyton Manning back on the field leading Nobel-Prize-worthy no-huddle comebacks. But can we thank stem cell research? Unlikely.

And on that note, we’re enjoying the giants victory and the cheering crowds outside our offices. And we’re looking forward to the day when stem cell therapies are available for both critical conditions like diabetes, blindness, and Altzheimer’s disease as well as for athletic injuries.


Relationship building in San Diego: Bringing investors into regenerative medicine

CIRM is cosponsoring the Investor and Partnering Forum at the Stem Cell Meeting on the Mesa in San Diego. It’s an effort to build relationships between investors, companies, and entrepreneurial academics.

Stem cells have been in the news a lot lately thanks to Nobel prizes and scientific discoveries. But for many biotech companies all the good news is scant consolation if they can’t get the money they need to do the research that’s required to bring promising therapies to market.

That message was driven home on the first day of the annual Stem Cells Meeting on the Mesa  at the Sanford Consortium for Regenerative Medicine in San Diego. It’s a gathering of some of the top scientific researchers, industry pioneers and investors. The goal is to bring together the leaders in the field to create new partnerships and advance stem cell science into cures. But when Robert Parlay, Chairman and CEO of stem cell manufacturing company Cellular Dynamics International, got up to talk to the audience and asked for a show of hands from all the investors in the room, only a few people in a room of a few hundred raised their hands.

It was a powerful visual indicator of just how difficult it is for even leading biotech and other companies to attract the investment they need. It’s also a reminder of just how important the stem cell agency is in filling that gap. Without our funding the picture would be even more grim.

Just last week the CIRM governing board approved almost $20 million in funding two biotech companies – ViaCyte, Inc. and bluebird bio – in the first round of our Strategic Partnership Award initiative (here’s our press release). It’s an effort to attract more industry engagement and investment into stem cell research.

Ron Leuty of the San Francisco Business Times recently interviewed Bluebird Bio chief medical officer David Davidson about the company’s CIRM funding. He said:

Partnering with California and our investigators in California is essential for the success of this study. California has more patients with beta-thalassemia than any other state. There are world-renowned experts in the field there who we are working with. This is really essential for the success of the study.

Stem Cells on the Mesa shows that there are many companies who would love to be more engaged, who would love to be able to do more, all they need is the money.

Many speakers at the meeting spoke out loudly in praise of CIRM and the funding we provide to help drive the most promising science towards clinical trials. Jonathan Thomas, CIRM Chairman, echoed those sentiments saying: “One of the things we talk a lot about at CIRM is how we can work even more closely with industry, helping companies advance the ball.”

That doesn’t just mean with funding from us but also with advice on how to navigate the regulatory process, how to work with the FDA, and how to partner with the big pharmaceutical companies who have access to enormous resources

“We are placing real emphasis on trying to get Big Pharma to work with companies earlier on in the process,” Thomas said. “We have Big Pharma coming to us, looking for introductions to the most promising work. We are happy to do that because it gives them access to good projects and gives the researchers and industry access to the funds they need to take their products to market.”

It’s exciting being at a meeting like this, filled with so many talented people who are passionate about the work they do and believe in the promise of stem cell research to deliver therapies and cures.

As Jonathan Thomas pointed out, events like this are a reminder why the people of California are so important to the future of stem cell research. Their support makes it possible for meetings like Stem Cells on the Mesa to take place, and possible for everyone involved to talk in terms of cures instead of lost opportunities.


Diabetes stem cell therapy moving toward clinical trials

Yesterday, at a meeting of our governing board – the Independent Citizens Oversight Committee (ICOC) – we were delighted to see a project we have helped nurture from a cool theory into a truly promising therapy head towards clinical trials in people. The ICOC approved funding for a ViaCyte stem cell therapy for type 1 diabetes as part of our new Strategic Partnership Award initiative.

This initiative is an effort to attract more engagement and investment from industry in stem cell research (we blogged about that initiative here). ViaCyte got more than $10 million. Bluebird Bio got $9.3 million for research into Beta-thalassemia, a potentially deadly blood disorder.

We have worked with ViaCyte on this therapy over several different funding awards and at different stages of development of the product. Now, it’s going into a critical phase, finishing off pre-clinical and starting clinical testing. You can see summaries of all the awards we’ve given to ViaCyte to-date, plus a summary of the Bluebird Bio award on our website.

After the governing board voted to approve the award, Paul Laikind, PhD, President and CEO of ViaCyte thanked the board and the people of California for making this possible, saying:

“You have allowed us to carry on our ground breaking research which we hope will transform the treatment of diabetes in California and around the world. Thanks to CIRM this could lead to therapies curing type 1 and helping those with type 2 diabetes.”

CIRM had Dr. Laikind said CIRM funding helped ViaCyte greatly increase the size of its workforce in California, and to use our support as leverage to attract even more funding from other organizations, including the European union. That means more money coming into the state, and more jobs for Californians.

What was also gratifying was to hear from Jason Gardner, PhD, head of Regenerative Medicine at global health care company GlaxoSmithKline (GSK). They are in negotiations with ViaCyte to help take this therapy through the rest of its clinical trial phase and, hopefully, through to FDA approval.

This would be the first time that one of our grantees has partnered with a global pharmaceutical company of the size of GSK on a product we have helped support. It is potentially a hugely important step. Dr. Gardner reflected on the value of those alliances when he said:

“We are aligned on three levels; that cell-based regenerative medicine can be transformative, that this path is complex and high risk, and that this is best shared by those who have shared goals.”

CIRM President Alan Trounson, PhD echoed those feelings when he said

“This is one of the most important steps we have taken here in terms of bringing these therapies to patients. To have a company, a major organization like GSK consider being a partner with us on a program we have shepherded through basic science into the clinic is validation of our program. I think this will resound throughout California and the US. I hope this will be one of those moments we can look back on and say this made Proposition 71 worthwhile not just for California but, I would say, for the whole world.”

That’s pretty heady stuff. But when you consider that worldwide almost 350 million people have diabetes, and those numbers are rising each year, then a therapy like this has the potential to change the world around us.

Last year we produced this video describing ViaCyte’s diabetes project.


UCLA scientist shares stem cell research with the next generation

CIRM grantee at UCLA Michael Teitell spoke with high school students on Stem Cell Awareness Day

Michael Teitell working with one of his lab students

When speaking with high school students one learns to always expect the unexpected. Such visits can be exhilarating and surprising and are never boring. I was asked to write a guest blog for CIRM because of a wonderful interaction I had recently with a biology class at Crescenta Valley High School in La Crescenta, California, as part of the CIRM sponsored Stem Cell Awareness Day. It is inspiring to talk to young people about stem cell research and the work we do at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. Yet, this visit was special because of the very open and interactive discussion the students and I had that day.

The students shared with me their knowledge of the basics of stem cell biology, so we skipped over the usual introductory material and instead we engaged in an in-depth discussion of the cutting edge work supported by CIRM, including research at UCLA’s Broad Stem Cell Research Center (those awards are listed here), and the potential real-world application of stem cell research in the development of treatments and cures for a wide range of diseases. Among the topics that particularly energized the students was that of induced pluripotent stem cells, by coincidence the discovery that resulted in the 2012 Nobel Prize for medicine a few days later.

One student wrote to me afterwards saying:

‘The thing that interested me most was {that Dr. Yamanaka} discovered how to take mature adult cells and turn them into stem cells. I find that backwards process fascinating. This presentation me consider an occupation in stem cell research.”

The students were surprised and fascinated to learn that tissue-specific cells such as skin or blood could be reprogrammed to be pluripotent stem cells. Their questions were sharp and thoughtful and I found them very curious about the subject. Some of the students said that our discussion inspired them to possibly seek careers in molecular biology and stem cell research. One wrote:

“Before today I had very little intuition about stem cells and was not really interested in that field of study. However, your lectures totally changed my attitude towards the topic. When I got home, I spent three hours on my computer researching about stem cells. Every website I opened just increased my interest about stem cells.”

Other questions dealt with life in college, getting into college, and the students asked about doing research, such as pursuing a career in biology. As a member of a college admissions board, I noted that getting into a college they wanted and doing well there depended upon more than just studying and getting good grades. The college admissions reviewers will want to see demonstrated leadership in extracurricular activities inside and outside of high school to help assess whether the students will be productive members of the academic community. For some of the students it was important to have an opportunity to see inside this college experience:

“I found your background information and advice about college very inspirational. I gained a better understanding about what college was like and what I need to do to get where I want.”

I received a flood of emails afterward, one from nearly every student. I was impressed by the maturity, thoughtfulness and sincerity of their responses.

As the students discussed the amazing advances we are making in stem cell research it was clear that they are inspired by science. In turn, I was inspired by these students as they potentially represent the next generation of scientists who will build on our many current discoveries and transform stem cell research into the discoveries and treatments of the future.

Michael Teitell, MD, PhD
Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research
Department of Pathology and Laboratory Medicine
University of California, Los Angeles

Women in science get a boost from women in online media

Astronomer Caroline Herschel was one of those to get full entry on Wikipedia.
Tielemann, 1829/W. J. Herschel/The Royal Society

As a former woman in science and a current woman in online media, a story from Nature this week struck home. They write about an edit-a-thon held by the Royal Society in London, which brought in 15 female editors to expand Wikipedia’s representation of women in science. It turns out that women are underrepresented both places – only 15% of Wikipedia editors are women.


Father of bone marrow transplant — first stem cell therapy — dies

By far the predominant stem cell therapy today is a bone marrow transplant. The 60,000 people who receive a transplant this year have Nobel Laureate E. Donnall Thomas to thank for the treatment.

Thomas, who died this week, began working on bone marrow transplants back in the 1950s, when the prevailing wisdom held that no human organs could be transplanted, much less bone marrow. An obituary in the Seattle Times quoted Thomas:

“In the 1960s in particular and even into the 1970s, there were very responsible physicians who said this would never work. Some suggested it shouldn’t go on as an experimental thing.”

When the millionth person receives a transplant this year, I’m sure that person will be grateful that Thomas ignored the conventional wisdom and continued those experiments.

A bone marrow transplant works because blood-forming stem cells in the bone marrow, taken from either from a donor or from the patient, are transferred to someone with leukemia or other blood diseases, and those stem cells replace the person’s diseased blood system with a healthy one. Since the 1970s, when the first transplant between unrelated people was successful, scientists have incrementally improved the risky technique and expanded its range of use.

CIRM is part of that expansion. Our grantees are developing new ways of genetically engineering the blood-forming stem cells before transplantation to fix genetic diseases like sickle cell disease or to make cells resistant to HIV. Other scientists are working with cord blood cells, which contain the blood-forming stem cells taken from a baby’s umbilical cord at birth. These cells, like adult blood-forming stem cells, have proven widely useful in treating a range of diseases.

Today, diverse stem cell types are now beginning to enter clinical trials. Neural stem cells from the brain, mesenchymal stem cells from bone marrow or fat, and cells generated from embryonic stem cells and reprogrammed iPS cells are among those that are either in or nearing clinical trials.

When Thomas’ work entered clinical trials in the 1950s and 1960s, nobody knew how many lives that controversial therapy would save. Fifty years from now, I wonder which of today’s prospective therapies will be as commonplace. We won’t know until stem cell scientists do as Thomas did: keep trying.

Here’s a good resource if you want to learn more about bone marrow transplants.

Here are resources to learn about research by CIRM grantees working towards bone marrow transplant therapies for sickle cell disease, HIV/AIDS, and SCID (bubble boy disease).


Who’s the boss of the brain? How stem cells repair damage

Tony Wyss-Coray

In addition to their usual job of creating new cells, stem cells in the brain turn out to be excellent managers. That’s according to CIRM-funded researchers at Stanford University, who have recently published a paper describing how stem cells in the brain control the behavior of other cells.

The work could help explain why stem cell transplants appear to improve brain function even when they don’t form connections with other brain cells.

The paper itself, which was published in the journal Nature Neuroscience, has a lot of talk about cells in the brain communicating via a variety of acronym-laden molecules. What it all comes down to is this: stem cells in the brain and the cells they create (with the cumbersome name “neural progenitor cells) are the managers of a vast army of other cells. Damage the stem cells and you disrupt how those other cells behave.

Bruce Goldman at Stanford University described the work in superhero terms in a press release. Imagine a group of cells in the brain whose job it is to swoop around cleaning up damage (these cells are called microglia). Most of the time, they are like Clark Kent, puny and inactive. But when the neural progenitor cells give the signal they puff up and go on the attack.

One thought has been that disorders such as Alzheimer’s and Parkinson’s as well as damage after stroke might result, in part, when those superhero cells aren’t properly called to action. This could explain why transplanting stem cells into brains of people with those diseases might help improve symptoms. It’s like dropping a good manager into a disorganized office. Where once other cells meandered about without purpose, the neural progenitor cells instill order and put those microglia to work.

Goldman also wrote an entry on Stanford’s blog about the work, which contains possibly the clearest description of neural stem cells and their progeny that I’ve read. He writes:

Neural stem cells get plenty of good press, and understandably so. They’re the matriarchal cells of the brain, from which spring all except one type of cell populating our most highly regarded (at least by itself) organ. They can remain in their primordial state for decades, languidly dividing just enough to replace their own numbers. Alternatively, they can spawn daughter cells that depart from the primordial state.

It’s the matriarchs’ daughters – so-called neural progenitor cells – that embark on committed differentiation pathways giving rise to nerve cells and other key brain cells. Given that lofty ambition, it’s not surprising that neural progenitor cells divide much more rapidly than their parents do, outnumbering neural stem cells probably by 1,000 to 1 or more.

It turns out that neural progenitors can do more than breed. They’re excellent managers, too.

This work was funded by a CIRM Basic Biology awards, which are intended to fund research that better explains how stem cells function. This study is a great example of why those awards are so valuable. It’s hard to convince the Food and Drug Administration to allow you to test stem cells in people if you can’t also explain how those cells are working. This research begins to get at why transplanted stem cells appear to work, and could help other researchers move closer to testing their therapies in people.

CIRM funding: Tony Wyss-Coray (RB2-01637)


Testing iPS cells in people? Not yet

This past week a story unfolded that ended with the dismissal of a researcher from the University of Tokyo who had claimed to be the first to test a therapy based on reprogrammed iPS cells in humans.

It all began last week when CIRM grantee and UC Davis scientist Paul Knoepfler blogged about research being reported by Hisashi Moriguchi. He chronicled the story on his website. New Scientist describes the situation:

In a poster presented at a meeting of the New York Stem Cell Foundation, Moriguchi – who claimed to work at Harvard Medical School and the University of Tokyo – described results from a trial in which cardiac muscle cells were grown from induced pluripotent stem (iPS) cells, and transplanted into six US patients with severe heart failure.

… This was surprising, given the safety concerns that surround iPS cells – adult cells that have been reprogrammed to an embryonic state. Support for the claim quickly disintegrated: within hours, Harvard released a statement noting that Moriguchi had no current affiliation with the university, nor any ethical approval to run a clinical trial.

The supposed results got a lot of attention at the time because Shinya Yamanaka had just shared the Nobel Prize for his role in discovering how to make those very iPS cells that Moriguchi was claiming to have tested. Yamanaka works part time at the CIRM-funded Gladstone Institutes.

The problem is that he never did inject those patients. This is a big deal in part because CIRM and other organizations have been very critical of clinics claiming to be offering stem cell “therapies” based on no clinical trial data (here’s more information about stem cell tourism). In the U.S., new therapy ideas have to be tested in trials approved by the Food and Drug Administration, and those trials also have to be approved by an Institutional Review Board at the institution participating in the trial. In this case, Harvard claimed that their IRB had never approved the research.

CIRM requires IRB approval for any clinical trial that involves our funds, just like we require institutional animal review board and stem cell review board approval for animal research or research involving human embryonic stem cells. We get those assurances before we issue funding and in our yearly progress reports from grantees.

These steps – institutional reviews, Food and Drug Administration reviews, controlled clinical trials – do take time, but they also ensure that once a therapy reaches patients it is likely to be safe. While we would all love to find a cure for any number of diseases tomorrow the hard fact is that good science takes time, there are no short cuts. In science as in life, if something seems too good to be true, it usually is.


Arlen Spector: Science Policy Driven by Evidence, not Rhetoric

Geoff Lomax is CIRM’s Senior Officer to the Standards Working Group

In August 2001, I was frantically working to put the final touches on my doctoral dissertation focused on ethical and policy considerations related to the use of genetic testing for disease risk. I always viewed the ethics policy discussion as rather nuanced and academic, so it was quite a surprise to hear President Bush state in his first prime time address that: Research on embryonic stem cells raises profound ethical questions. I knew nothing about the field of stem cell research at the time, but I decided to take notice given that research ethics had come to the forefront of the national policy discussion.

Sen. Arlen Spector

Sen. Arlen Spector

For an aspiring student of research policy, it was essential to follow how the discussion played out. I had experience in a number of state and national legislative campaigns and was keenly aware how rhetoric can trump substance in policy debates.

In 2001 -2002, the most substantive policy deliberations were taking place in the United States Senate. One senator in particular, Arlen Specter, stood out because of his cogent questioning designed to elicit answers to core policy questions. In a 2002 hearing Senator Specter focused on whether under the Bush policy there a sufficient number of stem cell lines available for the required research. It seem quite remarkable that so much attention was being given to whether particular cell lines were sufficiently robust for research on Alzheimer’s and Parkinson’s disease. One of the most striking aspects of these deliberations was Senator Specter’s effort to move past rhetoric and get a complete picture of the policy issues.

This quality in Senator Spector extended to all his work, as the Los Angeles Times noted in their obituary of Spector after his death this week. They wrote, “he habitually asked probing questions of nominees from both parties instead of succumbing to the rhetorical approach favored by his colleagues.”

He brought this probing approach to NIH budget deliberations to document the value of disease treatment and prevention. The result was a doubling of the NIH budget over five years and Francis Collins, director of the National Institutes of Health (NIH), described Specter to The Scientist as “a towering champion for biomedical research and the mission of the NIH.”

Former CIRM Governing Board chairman Robert Klein described Spector as a man of character and conviction. I hope one legacy of Senator Spector’s career is the conviction that issues of science and research policy should be informed by substantive deliberations. Science is fundamentally driven by rules of evidence, and science policy should be no exception.

Geoff Lomax

Getting approval for stem cell clinical trials: a step by step guide

Ellen Feigal, M.D. Senior VP for
Research & Development at CIRM

Trying to move a promising therapy from the lab into clinical trials in patients is one of the most challenging parts of any drug discovery process. But when that new therapy involves a stem cell or cell-tissue it can be doubly so. You are not only dealing with questions of whether it’s safe (always good to know) and whether it works (rather important too) but you are also dealing with a whole new area of science that adds extra questions and complications along the way.

That’s why CIRM teamed up with the Alliance for Regenerative Medicine (ARM) to come up with a new step-by-step guide on how to navigate the tough regulatory waters and get approval from the Food and Drug Administration to move a therapy into clinical trials. The result is a white paper published in the journal Stem Cells Translational Medicine.

It lays out precisely what a company needs to do, when, why and how if it wants to get FDA approval.

As Ellen Feigal, MD, CIRM’s Senior VP for Research and Development and the lead author of the article, points out in the paper:

“The field of regenerative medicine is still relatively young and involves new and novel science. The products involved might be classified as a biologic – such as human cells and tissues or gene therapy- a device, a drug or combination of those. They also span a range of areas from biology to chemistry and physics and so could come under multiple regulatory agencies. All that can create uncertainty and confusion. The goal of this paper is to help companies understand the complexity of the process and how to most effectively navigate through it.”

In our press release we quote Michael Werner, Executive Director of the Alliance for Regenerative Medicine, and a co-author of the study:

“Everyone involved in this process, whether it’s a company or the FDA, has a shared goal of bringing safe and effective therapies to the public as quickly as possible.”

The article is comprehensive but even with this information companies will face lots of challenges along the way But by helping take some of the uncertainty out of the process we hope to make it easier for companies to get their therapies where they are needed the most, in patients.