Stem Cell Awareness Day October 5, 2011

Stay tuned for a Stem Cell Awareness Day event near you. October 5 will bring stem cell lectures, tours and symposia to nearly 40 locations around the world. So far, there are events in six countries, five U.S. states and at least 25 locations in California, and more are being added every day. You can see a list of events on the website.

In addition to opportunities for the public to learn about stem cell research, CIRM grantees and staff are going into more than 50 high schools to talk about the field with high school students.

CIRM chair Jonathan Thomas is kicking off the event on October 4 from the World Stem Cell Summit in Pasadena where he’s hosting a reception for patient advocates. Throughout the meeting we will be posting to this blog short video interviews with patient advocates talking about their hopes for stem cell research. Watch for those starting next week.

If people are interested in hosting an event contact Chris Stiehl at chris@stiehlworks.com.

A.A.

Rolling back the clock on muscle disease, aging

Last week CIRM grantees at University of California Berkeley published a follow-up to some of my favorite stem cell research. I’m speaking personally here as a runner who is getting older and would like to turn my race recovery back to what it was in my youth.

Irina Conboy started investigating the slow response of aging muscle stem cells as a postdoctoral fellow in the lab of Thomas Rando at Stanford University (I’ve written about that work here). What they found is that older muscles in mice don’t respond very effectively to muscle damage. But, and this is a big but, if those older mice have younger blood, the muscle stem cells work just fine. Strange, but true.

Since that discovery, Conboy and her lab at Berkeley has been piecing together the story of how and why the younger blood refreshes those old and tired muscle stem cells. In their latest work, which was published in the journal Chemistry & Biology, they show a way using a short-term dose of chemicals to roll back the clock on mature muscle and return it to an earlier state.

A press release from UC Berkeley says:

Building new muscle to replace old or damaged tissue is the routine job of muscle stem cells, or satellite cells. Stationed along the perimeter of adult muscle tissue, they wait for a signal to grow, divide and fuse into new muscle fibers when there’s damage to repair.

But that repair process gets worn out in people with Duchenne muscular dystrophy, a genetic condition in which muscles degenerate because of a defective structural protein and subsequent exhaustion of muscle stem cells. Muscle repair also becomes incapacitated with advancing age.

The group hopes that by turning back the clock, they can return the muscle to a state where it is better able to repair damage. The press release goes on to say:

The researchers say the next steps include testing the process on human muscle tissue and screening for other molecular compounds that could help de-differentiate mature tissue.

“This approach won’t work for all degenerative diseases,” said Conboy. “It might work for some diseases or conditions where we can start with differentiated tissue, such as neurons or liver cells. But patients with type I diabetes, for instance, lack the pancreatic beta-islet cells to produce insulin, so there is no functional differentiated tissue to start with. Our approach is not a replacement for pluripotent cells, but it’s an additional tool in the arsenal of stem cell therapies.”

The group is a long way from marketing the next race recovery beverage. They still have to show that the technique works in human muscle and that those more youthful cells are better able to repair damage.

CIRM Funding: Irina Conboy (RN1-00532-1)
Chemistry & Biology, September 23, 2011

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San Diego stem cell community gets a boost from CIRM

The North County Times in had a nice story today about the effect of CIRM funding in the San Diego area. Bradley Fikes wrote:

In San Diego County, one of the country’s top three centers of biomedicine, researchers say CIRM has greatly boosted stem cell science’s profile and magnitude. That commitment is producing advances that will translate into patient health and an economic boost for the local life sciences industry, they say.

It goes on to discuss the new Sanford Consortium building that will open next month. The building received $43 million from CIRM, which the consortium used to leverage additional money to building the $115 million project that pulls together giants of the stem cell field from UCSD, Scripps Research Institute, the Salk Institute for Biological Studies, and the Sanford-Burnham Medical Research Institute. In addition to pulling great minds into one space, the building will contain research facilities that can be shared by member institutions.

As with all of the CIRM-funded buildings. The goal isn’t just to build fancy space. The goal is to speed research by pooling ideas, encouraging collaboration, and providing much needed equipment in convenient settings to speed research along.

The story goes on to say:

Over at the Salk Institute, veteran researcher Inder Verma says the state program catalyzed the institute’s involvement with stem cell research. The program paid for a shared laboratory at Salk devoted to stem cell technology. This “stem cell core facility” provides training and equipment for scientists interested in working with stem cells.

The core facility was especially important for those workingwith human embryonic stem cells, because of federal restrictions imposed by President Bush in 2001 on the use of its money for that research, Verma said. President Barack Obama relaxed those restrictions after taking office in 2009. The facility also works with artificial embryonic stem cells called IPS, or induced pluripotent stem cells, which are typically grown from skin cells called fibroblasts.

“Many people at the Salk wanted to work in this area, but they didn’t know where to start, because they didn’t have access to these cells, they didn’t have access to the technology,” Verma said. “But once we had a core facility, suddenly, a large number of labs, 16 to 17, began to do work in the area of regenerative medicine. My lab had almost no one working on stem cells, and now, there are six to eight people working on stem cells.”

San Diego is one of three major research centers in California where stem cell companies and academic labs have flourished. The other two are in Los Angeles and San Francisco. This interactive map shows where CIRM’s funding has gone.

A.A.

Progress in stem cell therapy for HIV/AIDS

Last week the company Sangamo Biosciences announced good results from their HIV/AIDS trial in which they genetically altered patients’ own T-cells. CIRM is following this trial closely, since it’s the precursor to one being developed by a team of CIRM-funded researchers led by John Zaia at City of Hope that includes Sangamo.

According to Discover Magazine, the company reported last week:

The goal was to see if receiving these altered cells would let patients go off their anti-retroviral drugs. The results, reported at a recent conference in Chicago, were mixed—the cells didn’t always survive long in the fifteen people enrolled. But two patients saw their HIV levels drop 10-fold, and one patient who stopped his anti-retrovirals first saw a spike in virus levels but then had them decline to undetectable levels.

The work funded by CIRM is a next generation version of this trial. In both cases, Sangamo’s technology is used to snip the DNA of cells taken from a patient’s bone marrow. Those snips introduce a mutation in a gene called CCR5, which makes the protein that the HIV virus uses to enter a cell. No CCR5 gene means HIV can’t infect the cells.

Doctors then reintroduce those cells into the patient. The idea is that the patient will then be resistant to the HIV in their bloodstream and eventually can go off drugs. In the recently reported study, the team altered the adult T-cells, which would supply a finite number of resistant T cells. The CIRM study will be altering the blood-forming stem cells, which give rise to T-cells, in hopes of creating a more permanent supply of HIV-resistant T-cells.

This video gives more information about the goal of the CIRM-funded team:

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More stem cell firsts — spinal cord injury and blindness

Tuesday was a very proud day here at CIRM headquarters. We were able to announce the enrollment of the first patient in a clinical trial funded, in part, by the agency. It was also a bit of a somber day as Paul Knoepfler pointed out in his blog yesterday. It meant the patient had recently undergone a life-changing tragedy that landed them in need of the hope the follow-on trials to this safety study might provide.

This morning’s news feed brought a similar double-edged milestone. Stem Cells Inc, the Newark California-based biotech firm, announced that the day before their research team had injected adult neural stem cells into a spinal cord injury patient for the first time. The stem cells were administered at Balgrist University Hospital of the University of Zurich to a 23-year old German man who had suffered a spinal cord injury in an auto accident in April and was completely paralyzed below the waist.

A press release from the company posted on Yahoo has a quote from the patient that vividly points out the double-edged nature of this milestone to him:

“This terrible injury crossed out almost all my life plans, and has led me to an unexpected path. Participating in this clinical trial not only gives me a sense of hope, but it also helps move this important research forward.”

There was another strong linkage between these two milestones. One of the lead surgeons at the Zurich hospital was Raphael Guzman who has a visiting appointment there and is on faculty at Stanford, where he is a colleague of Gary Steinberg who transplanted the cells in the CIRM-funded trial at Santa Clara Valley Medical Center.

Today’s news feed brought a third milestone to our field. Advanced Cell Technology (ACT) announced that they had been given approval to begin the first clinical trial of cells derived from embryonic stem cells in Europe. They will be testing cells for a form blindness that strikes children called Stargardt’s disease. Clearance to begin the trial came from the United Kingdom Medicines and Healthcare Products Regulatory Agency.

ACT launched a similar trial in the US in November 2010 and a second trial in January, this one for macular degeneration, the leading cause of blindness in the elderly. This summer the company announced the first patients were enrolled in each trial at UCLA in July.

Robert Lanza, chief scientific officer at ACT told a news organization in the UK in this morning’s coverage:

“We’re very pleased with the results so far. We’re in the process of scheduling the next two patients for each of the two (US) trials.”

We are keeping our fingers crossed that this early track record for safety holds.

DG

First patient enrolls in a clinical trial funded by CIRM

Today is a landmark day for CIRM: We announced that the first patient had been enrolled in a clinical trial based on stem cell agency funding. You can read our press release here.

The patient was part of Menlo Park-based Geron’s phase I trial for spinal cord injury, which was awarded $25 million from CIRM in May. Stanford neurosurgeon Gary Steinberg, MD, PhD, implanted the cells Sept. 17 at Rehabilitation Trauma Center at Santa Clara Valley Medical Center.

Stanford had this to say about the trial:

Researchers at Geron collaborated with Hans Keirstead, PhD, and his laboratory team at UC-Irvine to develop a way to coax human embryonic stem cells to become a mixture of cells that include oligodendrocyte precursors. Oligodendrocytes are cells in the brain and the central nervous system that wrap nerve cells with an insulating material called myelin. This myelin sheath is necessary for the transmission of the electric signals along the spinal cord that trigger muscles to move, and relay our sense of touch and temperature. Damage to this sheath caused by trauma is a common cause of paralysis.

To be eligible for the trial, patients must have recent (within 14 days of injury) non-penetrating damage to a specific region of their thoracic spine — an area roughly from the top of the shoulder blades to the bottom of the rib cage. The damage must cause complete paraplegia, meaning that they have normal sensation or movement to the level of the hands, but not from the trunk to the toes.

During the procedure, Steinberg applied about 2 million of the special cells, called GRNOPC1, directly into the injured area of the patient’s spinal cord.

“We are quite pleased that the surgery was completed successfully and the patient is doing well,” said Steinberg.

When the CIRM governing board voted to fund the Geron trial, spinal cord injury advocate Roman Reed wrote a guest blog entry in which he said:

In a truly historic partnership for stem cell research and cure, state funding from what has been called “Roman’s Law” gave Hans Keirstead the seed money to achieve empirical evidence and proof of principle. Hans then sold his pioneering technique to Geron, and advanced biotechnology farther by founding California Stem Cell with the proceeds.

With admirable courage and determination, Geron pushed this science all the way to FDA approval to become the world’s first embryonic stem cell derived human clinical trial.

Now our beloved state agency, the California Institute for Regenerative Medicine will provide funding to bring about a full and complete Human Clinical Trial!!

The Keirstead/Geron/CIRM Trials advances the entire field of stem cell research.

Today’s announcement marks a milestone that is a critical step toward making safe and effective stem cell-based therapies available to patients.

A.A.

Meeting of California’s stem cell minds

Last week CIRM held our almost-yearly grantee meeting, which brought together our grantees from across California plus some international collaborators and world-renowned stem cell leaders who gave some riveting talks.

CIRM grantee Paul Knoepfler from UC Davis was blogging from the meeting. He had this to say:

Earlier I threw out there the idea that many different interested parties should come together to advance science. Something I called “big tent science” and “big tent team science”.

I think CIRM is an outstanding example of this idea in action and I could see that in evidence today at the CIRM Grantee Meeting here in San Francisco. It’s very inspirational.

He went on to share this from a talk by Craig Ventor:

The meeting was kicked off with a talk by Craig Venter, the amazing scientist who has pushed research forward in so many ways including sequencing the human genome and making the first synthetic life form.

Dr. Venter, who has been involved in some of the most cutting-edge, exciting science in the last century as well as founding or being involved in many scientific organizations, said this about CIRM:

“This is the greatest scientific organization founded in our era.”

Being there what stood out was the wide range of diseases being studied by our grantees, all with the eventual hope of finding therapies. It’s a real thrill to see signs of hope for the wonderful patient advocates I’ve gotten to know through CIRM, and for my friends and family, all of whom stand to benefit from this work.

We’ll be posting more about the meeting, including videos of two talks (including Ventor’s) and of a pre-meeting target product profile workshop,  and a video montage of our grantees talking about their work.

A.A.

UCSF stem cell building: generating therapies and making news

The new UCSF stem cell building has made the news again. The September 19 issue of The New Yorker, architecture critic Paul Goldberger features UCSF’s Ray and Dagmar Dolby Regeneration Medicine as one of three new science buildings in the United States “crafted with the specific intention of fostering interaction and connections, as a means of generating ideas.”

A press release from UCSF says:

Constructed on what Goldberger called an “eye-poppingly impossible site,” the building is home to some 300 scientists studying the earliest stages of cell and tissue development, with the goal of understanding and developing cell-based treatment strategies for such diseases as heart disease, diabetes, epilepsy, multiple sclerosis, Parkinson’s disease, Lou Gehrig’s disease, spinal cord injury and cancer.

This is one of the buildings CIRM partially funded back in 2008, when the agency realized that a critical component of generating new therapies was providing scientists with a place to work. CIRM’s investment of $271 million leveraged $560 million from private donors and $322 million in commitments from the institutions themselves. UCSF has this to say about funding for the building:

The $123 million building was paid for with state and private funds. In 2006, Ray and Dagmar Dolby contributed $16 million to launch the university’s fundraising campaign for the facility. In 2007, UCSF received a highly competitive $34.9 million grant from California Institute for Regenerative Medicine (CIRM). In 2008, UCSF received a $25 million grant from The Eli and Edythe Broad Foundation.  Last winter, UCSF received an additional $20 million donation from the Dolbys. The university has $12 million left to raise.

When Eli and Edythe Broad made their donation to UCSF CIRM made this video about our hopes for the stem cell buildings:

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Alzheimer’s leader discusses stem cell progress

Tom Vasich at the University of California Irvine did a Q&A with CIRM grantee Frank LaFerla in advance of the September 30 Southern California Alzheimer’s Disease Research Conference. La Ferla and his colleagues have been working on stem cell-based therapies for Alzheimer’s disease.

In a question about the public health impact of Alzheimer’s disease LaFerla said:

It’ll be enormous, especially locally. California has the nation’s largest baby boom population; Orange County by itself ranks fifth. Alzheimer’s is going to hit us hard, because age is the most significant risk factor for the disease. One of every 20 people over 65 will be affected by dementia, and eventually half of those over 85 will suffer from Alzheimer’s. This is going to put an amazing strain on our healthcare system and on families.

He went on to talk about his own research, funded by CIRM:

We’ve had a lot of success with animal models showing that neural stem cells can reverse Alzheimer’s-like cognitive deficits. We’ve progressed to creating a population of human neural stem cells that will be the basis of clinical trials on patients. We’re still in the early stages, and we’re fortunate to have received a grant from the California Institute for Regenerative Medicine that is supporting our work.

We had the pleasure of talking to LaFerla about this week a few years ago. In this video, he describes the work and the importance of finding a therapy for the disease.

A.A.

Stem cells from rhino skin

Northern White Rhinoceros; Photo credit: San Diego Zoo

What are those rhinos doing in a stem cell blog? Researchers at Scripps Research Institute have converted skin cells from those rhinos (or their San Diego zoo-mates) into reprogrammed stem cells. The team also created stem cells out of skin samples from a primate called a drill.

Both projects came out of conversation between Oliver Ryder, the director of genetics at the San Diego Zoo Institute for Conservation Research, and Jeanne Loring, professor of developmental neurobiology at Scripps Research and CIRM grantee. Ryder’s team had already established the Frozen Zoo, a bank of skin cells and other materials from more than 800 species and wondered if the thousands of samples they had amassed might be used as starting points.

The group, which includes an intern from the CIRM Bridges to Stem Cell Research program, published their work in the September 4, 2011 advanced online edition of Nature Methods. According to a Scripps press release, the work has the potential of preserving and even strengthening populations of endangered animals.

One of the greatest concerns with small populations such as the northern white rhinos is that even if they did reproduce, which hasn’t happened in many years, their genetic diversity is inevitably and dangerously low, and such inbreeding leads to unhealthy animals.

But researchers are moving toward inducing stem cells to differentiate into sperm or egg cells. With that accomplished, one possibility is that scientists could take skin cells in the Frozen Zoo from long dead animals, induce pluripotency, trigger differentiation into sperm cells, and then combine these with a living animal’s eggs through in vitro fertilization. Otherwise-lost genetic diversity would then be reintroduced into the population, making it healthier, larger, and more robust.

Or, both eggs and sperm might be produced from the stem cells, with the resulting embryos implanted in live animals, a process that current research suggests could be much more reliable than existing cloning techniques.

Scientists are already exploring the possibility of producing sperm and eggs from stem cells as a potential solution to human infertility issues. Loring hopes that some of these groups might consider initial technique development using endangered species stem cells. “I think that work would be a lot easier ethically with endangered species than with humans,” she said, “so I suspect some people working in this area would love to have our cells for experiments.”

The press release goes on to quote Ryder:

“The best way to manage extinctions is to preserve species and their habitats, but that’s not working all the time.” The rhinos are a perfect example, he said, because there are so few. “Stem cell technology provides some level of hope that they won’t have to become extinct even though they’ve been completely eliminated from their habitats. I think that if humankind wants to save this species, we’re going to have to develop new methodologies.”

CIRM funding: Susanne Montague (TB1-01186)

- A. A.