CIRM-supported high school student Amy Thakrar carrying out a stem cell research project in the lab of Joel Rothman lab at UC Santa Barbara

Janet Napolitano became the president of the University of California system on September 30 and yesterday, in her first major speech in the role, she pledged $15 million for training programs. The funds came out of the system’s “unrestricted” funds—read stash for favorite projects.
We are thrilled that training rose to the top of her priority list. This commitment matches CIRM’s. Our first grants in 2006 were for training graduate students, post doctoral fellows and clinical fellows.

Napolitano, former secretary of Home Land Security, committed $5 million each to programs to fund tuition for students in the country illegally, support for graduate students and support for post docs. The San Francisco Chronicle ran a story about her speech and quoted her on the importance of graduate students and post docs, saying:

“(they) are our future faculty members. They are our future innovators. They are our future Nobel laureates. They merit our additional support right now.”

Dismissing talk of taking the massive $24 billion system private with its 10 campuses and five medical centers, she instead affirmed the valuable role the UC system plays for the state:

“My intent is to be the best advocate possible for what this university and this state can achieve together.”

That, too, is CIRM’s goal, working to be a valuable part of California. Since those first training grants in 2007, we have committed $131 million to supporting graduate students and fellows. But we also believe that training is a continuum that stretches from high school to junior faculty positions. CIRM has awarded more than $370 million to our programs that span this pipeline for the intellectual infrastructure of California’s world-leading stem cell community.

We have internships for high school students, a seven-unit high school curriculum, a program for undergrad internships, and a program to support the early years of new faculty.

Don Gibbons

On October 1st, CIRM along with the AIDS Research Institute and the Gladstone Institutes hosted an inspiring public forum in San Francisco about the current state of HIV cure research. If you were not among the 100+ in attendance, not to worry, today we posted video recordings of the event on our website or you can watch them above.

I highly recommend the videos, which include brief talks and a panel discussion by a distinguished lineup of clinicians, researchers and advocates, many of whom have dedicated their life’s work toward finding a cure for HIV infection. My colleague Don Gibbons also wrote a very insightful blog about the town hall event which include his personal reflections about the search for a HIV cure.

Although antiretroviral therapy has dramatically extended the life of HIV infected individuals, the life-long daily regimen of pills is not a cure. The drugs’ side effects lead to various complications such as increased incidence of heart disease and cancer that significantly reduces lifespans. Not to mention the fact that of the 26 million HIV positive individuals who need treatment, 17 million of those don’t have access to antiretroviral therapy. As Warner Greene, director of the Gladstone Institute of Virology and Immunology, mentioned during the panel discussion:

The only hope for Africa is a cure because the world is not able and not willing to put the money forward that’s necessary to put everybody [HIV positive individuals] for the rest of their lives on antiretroviral therapy. It’s a huge number. So the cure is absolutely essential for Africa. So therefore whatever the cure is, it has to be scalable, it has to be safe and it has to be usable in the developing world. 

Based on these realities, the recent isolated reports of individuals being cured of HIV infection have brought a lot of excitement as well as cautiousness. That’s what motivated this forum: to provide an interface between HIV experts and the community to ask, are we there yet with a HIV cure? As Jeff Sheehy states in his introductory remarks during the forum:

The great news is these reports of a cure are real. But the sobering news is that making a cure that’s safe and available for most people with HIV remains a significant challenge. A huge challenge. But importantly the proofs of concept that are provided by the case reports have made it possible for us to seriously think about and actually seriously work towards developing a cure that will one day work for most people with HIV. Our goal [during this forum] is to engage the community, initiate a dialogue, clear up some of the misconceptions, tamp down some of the hype and some of the hype has been absolutely crazy. But I want to note that we can be realistically hopeful that there are solid grounds for pragmatic optimism.

In addition to these videos, also visit our HIV/AIDS fact sheet to learn more about CIRM-funded projects related to HIV research.

Todd Dubnicoff

OK, so I admit we’re biased, but we at CIRM have to agree with UC Davis researcher and CIRM grantee Paul Knoepfler, who makes a case on his blog for CIRM’s many benefits to the state. New jobs, tax revenues, revolutionary science and all that.

“There is no stem cell crystal ball so as with anything there are risks and uncertainties, but I believe that in the end CIRM 2.0 will keep California the global stem cell leader with the potential for huge benefits to the state as well as patients and medicine around the world.”

CIRM is in the process of figuring out the best way of continuing to serve the state after our initial funding runs out in a few years. Many of the projects that we have funded are close to clinical trials and we would hate to see such promising research wither on the vine due to a lack of financial support. And, as Knoepfler points out, we’re in the process of finding a new president to replace Alan Trounson, who guided us so ably through the critical last five years.

The end result of both of those searches we hope will result in the CIRM 2.0 that meets the vision Knoepfler lays out (and, we dare add, the vision of those voters who created the agency back in 2004): an agency that leads the world in driving new stem cell-based therapies and that creates an economic engine for the state.

Between now and whenever decisions have to be made in a few years our focus is on helping make sure our most advanced projects start clinical trials and reach patients. We’re funding clinical trials now in HIV/AIDS and heart disease and expect to see trials start for our projects targeting diabetes, forms of cancer, blindness, sickle cell disease and others.

Amy Adams

This week the Michael J. Fox Foundation asked whatever happened to stem cells? We could have told them: a lot has happened with stem cells in Parkinson’s disease. Just look at our Parkinson’s disease fact sheet.

But instead of asking us, Dave Iverson asked Brian Fiske, PhD, vice president of research programs at MJFF and Olle Lindvall, MD, PhD, chairman of the Division of Neurology at the University Hospital in Lund, Sweden and MJFF scientific advisor about stem cell research for Parkinson’s disease and put a podcast of the conversation on their blog.

The conversation is a good overview of approaches scientists are taking, and hurdles they currently face. When asked what gives him hope, Lindvall answered:

“Well of course the dream scenario is that first these cellular models will give us a better idea of what is causing Parkinson’s disease, the death of the dopaminergic neurons. That’s of course one aspect. The other is that we will within the next couple of years be able to use cells generated from stem cells, dopaminergic neurons, for implantation into Parkinson’s patients and that that will give a therapeutically valuable and clinically competitive treatment for the motor symptoms.”

For more on stem cell approaches to treating the disease watch our Parkinson’s disease Ask the Expert video, which also discusses the many approaches our grantees are taking. 

Amy Adams

French anthropologist Claude Levi-Strauss once said: “the scientist is not a person who gives the right answers, he’s one who asks the right questions.” That’s how science progresses, a never-ending series of questions to make sure that what you think is right, is right.

That’s why there are so many scientific conferences. They bring together some of the finest scientific minds of the day in any particular field to pose tough questions, and to question the answers. That’s particularly important in a relatively young field such as stem cell research. We have come a long way in a short time in improving our understanding of how stem cells work but clearly we still have a long way to go to fully understand how to harness those cells and use them to repair damage and restore health.

That’s why the stem cell agency is teaming up with the World Alliance Forum to hold a conference entitled “Future of Stem Cells” on November 15 in San Francisco. The event brings together two Nobel Prize winners (Dr. Shinya Yamanaka and Dr. Paul Berg) and some of the sharpest minds from academia and industry to explore the most pressing questions in stem cell research today.

The forum will discuss the most promising advances in stem cell technology as well as the challenges that need to be overcome before that promise can be turned into practical applications. It also features some biotech industry leaders that are working hard to turn theory into practice, such as Cellular Dynamics International (which is a key partner in our iPS Cell Bank initiative) as well as CIRM-funded iPierian and StemCells Inc.

Autodesk, Inc. – a 3D printing and design company based in Mill Valley – will also participate, highlighting a fascinating intersection of regenerative medicine and another industry. And because regenerative medicine will almost certainly change the face of medicine as we know it today another hot topic at the conference will be the societal impact of stem cell technology.

UC Davis stem cell researcher and blogger Dr. Paul Knoepfler calls the conference a “once in a lifetime kind of event.”

You can see a full list of speakers, topics and find out how to register for the event at http://wafsf.org.

Kevin McCormack

The votes are in, the decision has been made. UC Davis stem cell researcher, CIRM grantee and avid blogger Dr. Paul Knoepfler has named the winner of his Stem Cell Person of the Year award. And for the second year in a row it’s not me.

This year the winner is Dr. Elena Cattaneo the Director and Co-Founder of the Unistem, the Centre for Stem Cell Research at the University of Milano, Italy. Her lab specializes in working with brain cells to help develop new therapies for Huntington’s disease.

Paul announced the news on his blog saying:

“Beyond her great achievements in stem cell science, she is that rare stem cell scientist who goes well above and beyond the call of academic duty to act as an advocate as well.”

Dr. Cattaneo does not shy away from controversy. Earlier this year she took a very public stand against a new Italian law that would have allowed patients to get access to new and unproven stem cell therapies (we blogged about that law here). She decried the law saying:

“Irrational and unverified stem cell treatments based on methods that are not validated or scientifically documented should not reach patients. Preventing this from happening is a specific responsibility of health authorities and governments worldwide to make sure that the hope and trust of patients are not misused. Patients can be harmed and killed by medicines that have not been proven to be safe and effective via rigorously controlled clinical trials. The use of medicines that have not been manufactured to the highest possible standards is irresponsible.”

Cattaneo beat out a dozen other well known individuals – including Robert Lanza of ACT, Pope Francis and the stem cell agency’s own Dr. Pat Olson – to win the award.

Her prize is $1,000 and the recognition that comes with the award as someone who has made a positive impact on stem cell research.

Not only is she a fine researcher, she is also a generous person. She told Paul Knoepfler she intends to use the money to support a trainee scholarship to a future stem cell conference.

Congratulations to Dr. Cattaneo, and to Paul Knoepfler for another inspired choice.

And he assures us it’s not just an excuse to go to Italy to award the prize in person.

Kevin McCormack

With all our talk about finding new therapies for people it’s sometimes easy to lose track of the kind of very basic research that it sometimes takes to develop those therapies. And by very basic what I’m talking about in this case is yeast.

Yes, yeast are a long way from being human. And yes, they don’t exactly suffer the recognizable symptoms of a condition like Parkinson’s disease. But what they do is divide quickly and produce a lot of protein that scientists in a lab can then study.

Take the protein alpha-synuclein, which builds up and forms clumps in the brains of people with Parkinson’s disease. Scientists can’t just poke around carrying out experiments in a person’s brain, so instead a group at Whitehead Institute for Biomedical Research turned to yeast designed to over-produce that same protein.

It turns out yeast don’t like excess alpha-synuclein clumps any more than humans do. The cells turned sickly when they cranked out the extra protein.

The scientists could then expose these cells to different compounds to find ones that restored the yeast to health. They found one such compound, which they then tested in tiny roundworms and then in rats, which also produced excess alpha-synuclein. In each case, the compound helped the animals clear out the excess protein. They reported this findings in the journal Science.

But what about humans? The group took skin samples from people with Parkinson’s disease and created reprogrammed stem cells out of those samples. When those stem cells matured into brain cells, they showed symptoms of Parkinson’s disease. The compound they’d found in the lowly yeast improved symptoms in those cells.

The scientists stress that their compound is far from being a drug. They have a lot of work to do showing that it–or a compound with similar functionality–might be safe to test in people. But the scientists might not even be this close if they hadn’t started the search in the lowly yeast. A story in the Boston Globe quoted Vikram Khurana, who was one of the study’s authors:

“It was a real surprise. We would have had no clue about this target if we hadn’t had yeast genetics to show us the way.”

Amy Adams

Human mesenchymal stem cells being grown on a scaffold as a way of repairing bone. University of Cambridge on Flickr

Among the many injustices of aging: just as our tissues start falling apart, so to, our stem cells stop functioning as well to alleviate the damage. It just isn’t fair.

Muscle stem cells don’t respond as well to the cries of injured muscle tissue, and blood-forming stem cells in the bone marrow become prone to forming the wrong assortment of cells, not to mention accumulating mutations that lead to forms of leukemia.

Now, a group at Tulane University has shown that another group of stem cells lose their potential over time–the so-called mesenchymal stem cells. They published their work in STEM CELLS Translational Medicine.

Mesenchymal stem cells (or MSCs) live in the bone marrow and fat and can mature into bone, cartilage and fat tissue. They also migrate to areas of the body where they seem to tame immune reactions. They are being studied by scientists working to develop therapies for bone or muscle disease in addition to autoimmune diseases like rheumatoid arthritis and multiple sclerosis. The idea is that the cells will be able to calm the immune reaction that leads to those diseases.

The team of researchers from Tulane were specifically trying to use MSCs to treat people with multiple sclerosis, and wanted to investigate the performance of cells from older versus younger people. They took MSCs from people older than 60 and from people younger than 35 and tested them in mice with an induced autoimmune disorder that mimics MS.

Lo and behold, the mice that received the stem cells taken from older people developed significantly advanced disease compared with those receiving the younger cells.

The team isn’t saying that older people are just out of luck when it comes to possible MSC therapies that may be developed. But they do think they and other scientists have some work to do understanding how those cells age and finding ways of making the cells from older people more effective. A press release from the journal quotes Bruce Bunnel, who led the work:

“The most interesting question to me that came out of this is what is aging doing that is changing these cells? What is going on in the biological environment in the human body that is changing these cells? If you can figure that out, you may be able to improve the quality of these cells.”

Amy Adams

Several of our grantees are working on projects that involve destroying the stem cells at the heart of cancer. These cancer stem cells are a bit of a mind-bender: We’re used to thinking of stem cells as a good thing — they regenerate damaged tissues in our bodies. But cancer stem cells constantly regenerate the cancer. Destroy those stem cells and, we hope, you destroy the cancer.

One challenge for our grantees and for others has been that stem cells for different kinds of cancer have different properties, and it’s been hard to both find them and figure out how to kill them. Some scientists funded by the Broad Institute have taken another step toward solving this problem for acute myeloid leukemia stem cells.

The work, published in Nature Chemical Biology, provides a new way for scientists to mimic the cancer stem cell’s normal home in the bone marrow, then screen drugs to find ones that destroy the cells. A press release from the Broad Institute describes the findings:

After using the new system to screen more than 14,000 compounds, roughly a dozen were found that inhibited malignant stem cells and overcame the protective effects of stromal cells, while sparing healthy stem cells in a related screen. Several of the compounds were already known to inhibit leukemic cells, bolstering the validity of the model. The researchers further showed that many of the compounds could not have been found through traditional screening in cell lines, suggesting that the compounds are exerting their effects through more physiologic biology modeled in the novel system.

There’s more on our website about cancer stem cells and our grantees who are also looking for ways to destroy these cells in forms of leukemia.

Amy Adams

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun. 

Renee Reijo-Pera and Bertha Chen

Stem Cells for urinary incontinence. Fellow stem cell blogger, Don Reed, wrote a nice piece for the Huffington Post on some very promising work on urinary incontinence by CIRM-funded researchers at Stanford. Don clearly details the problem—seven million women in California alone impacted—and the current therapies and their shortcomings. He then explains how the two-woman team plans to grow muscle cells from stem cells and inject those directly into the urinary sphincter hoping they can strengthen that opening, which is the cause of most urinary leakage. Our web site contains more information on the project that will use reprogrammed iPS stem cells for incontinence.

ALS nerves in a dish yield therapy candidate. We often write about our ability to make iPS type stem cells from the skin of a patient, turn those cells into the tissue impacted by a disease, use those cells to understand the defect and test potential therapies. However, we are often detailing projects that have accomplished a couple of those steps.

This week a CIRM funded team at Cedars-Sinai in Los Angeles reported completing all those tasks with cells from a patient with the most common form of inherited ALS, Lou Gehrig’s disease. They replicated the disease, analyzed it, verified the defect and treated it. They found the defect causes a buildup of the intermediate form of genetic code knows as RNA, and verified that this buildup becomes toxic to the motor neurons. They then used a genetic trick called an antisense molecule to stop the excess buildup and get rid of what was already there. The work was published in Science Translational Medicine and a detailed press release from Cedars was posted to EuekAlert.

The release notes that CIRM funds a team hoping to begin a clinical trial with another approach to treating ALS. You can read about that project and others we fund on our ALS information page.

Another reason to love iPS—study evolution. With evolution denial creeping into the high school curriculum in a few states, I have to applaud any discovery that helps us study the underpinnings of evolution. Human genes seem to be more stable than the genes from lesser primates, but no one has known why.

Since iPS technology allows us to reprogram adult tissue into stem cells that can be grown long-term in the lab, researchers can now compare living cells from humans and non-human primates. In the current study, a team at the Salk Institute in La Jolla is comparing our genes to those in chimpanzees and bonobos. The team looked at the activity of “jumping genes,” which earn their name because they literally shift around in the chromosomes and in doing that can cause changes in neighboring genes. They found human cells had a much lower level of jumping gene activity. That could explain the relative stability of our genetic material. They published the paper in Nature and it was described on the web site HEALTHCANAL.

First windpipe holding up over time. Five years ago, a team in Barcelona for the first time implanted into a patient an artificial windpipe engineered with stem cells. They used the patient’s own stem cells seeded on the windpipe of a human donor that had been stripped of its soft tissues so that it was just a scaffold.

It was a pleasure to read in several outlets this week stories telling that the patient is doing well and leading a normal work life. The researchers published the update in Lancet and US News & World Report was one of many sources reporting the good news.

Stem cells and infant eye disease. Underdevelopment of the optic nerve is the leading cause of blindness in children and there are no effective therapies. That unmet need has driven many families to go to clinics in China that are offering treatments with umbilical cord blood. The claims of benefit from those clinics have been difficult to verify because children with the condition do sometime have spontaneous, but often transitory, minor improvement in vision.

One of the most well known of those clinics, Beike Biotech, agreed to let researchers at Children’s Hospital Los Angeles monitor 10 of its patients in China and compare them to untreated control patients back in Los Angeles. The Chinese clinic was only able to recruit two patients during the study period, but those patients showed no differences in a number of subjective and physical measurements compared to the controls. This is the type of comparative trial that needs to occur for most therapies being offered by unregulated clinics. The team published the results in the Journal of the American Association for Pediatric Opthalmology and Strabismus and it was covered by ScienceDaly.

Don Gibbons