CIRM grantee Alvarez-Buylla wins 2011 Prince of Asturias Award for neural stem cell research

Arturo Alvarex-Buylla, PhD

CIRM grantee and UCSF professor Arturo Alvarez-Buylla, PhD, won the prestigious 2011 Prince of Asturias Award for Technical and Scientific Research for his work with neural stem cells. He is credited with first discovering the regenerative cells in the brains of mammals, work that laid the groundwork for a number of CIRM grants and clinical trials based on neural stem cells.

In their announcement about the award UCSF quotes Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF.

“Arturo’s contribution to the field of adult stem cell science has been tremendous. He has helped lay the foundation for our understanding of the role and behavior of neural stem cells in the adult brain, which could lead to new strategies for treating brain damage and diseases.”

In the announcement, Jennifer O'Brien describes the work that earned Alvarez-Buylla his recognition:

Alvarez-Buylla, specifically, was recognized for identifying neural stem cells in the brains of mammals, and for his ongoing research on their behavior – and potential therapeutic use – in treating diseases. He is exploring their possible role in the development of the most common type of brain tumor, the glioma, and their potential use in regenerating brain tissue damaged by injury or degenerative diseases. More generally, he is studying the way in which adult neural stem cells behave and function – their development into young neurons, the migration of these neurons from their site of birth to their final destinations, and their function in the adult brain.

Alvarez-Buylla has a CIRM Early Translational II Award to develop a cell-based therapy to inhibit the hyperactive neural circuits in people with epilepsy. In his public summary for the award he writes:

In 20-30% of these patients, seizures are unresponsive to drugs, requiring invasive surgical resection of brain regions with aberrant activity. The candidate cells we propose to develop can inhibit hyperactive neural circuits after implantation into the damaged brain. As such, these cells could provide an effective treatment not just for epilepsy, but also for a variety of other neurological conditions like Parkinson's, traumatic brain injury, and spasticity after spinal cord injury.

It's great to see CIRM grantees honored for the incredible advances they've in medicine and human health.

A.A.

CIRM grantees convert skin to nerves, a step toward therapies for neurological disease

Last year a group of CIRM grantees at Stanford University directly converted mouse skin cells into neurons, bypassing the need to first convert those cells into an embryonic-like state. Now they've gone a step farther, pulling off the same feat with human cells. They published the work in the May 26 Nature.

Krista Conger at Stanford University blogged about that work , quoting senior author Marius Wernig:

We are now much closer to being able to mimic brain or neurological diseases in the laboratory. We may perhaps even be able to one day use these cells for human therapies.

This past year has seen a number of scientists managing to convert adult cells directly into other adult cell types as we blogged about here. Recent reports about immune rejection of iPS cells makes this work even more interesting because the direct conversion bypasses the need to create iPS cells. As Conger writes:

Interestingly, this direct conversion technique may offer a way around the recently reported rejection of genetically identical iPS cells by laboratory mice. That unexpected finding, which I blogged about a couple of weeks ago, has researchers worried about the potential therapeutic value of the cells. But preliminary investigations suggested that the immune response was targeted at proteins used to make the original cells pluripotent, which shouldn't be an issue with this approach.

That said, Wernig isn't ready to give up on iPS cells. He's part of a CIRM disease team that aims to use genetically modified iPS cells to treat the deadly skin condition epidermolysis bullosa. Here's a link to a summary about that epidermolysis bullosa disease team award, and a link to a videos of the team describing their approach to the CIRM governing board last year.

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Guest blogger Alan Trounson — May’s stem cell highlights

Each month CIRM President Alan Trounson gives his perspective on recently published papers he thinks will be valuable in moving the field of stem cell research forward. This month’s report, along with an archive of past reports, is available on the CIRM website.

The first paper I highlight in this month’s summary, purporting to have found master lung stem cells, is already generating controversy. (See our blog entry: Lung stem cell found, controversy ensues) Scientists have generally not been believed that one set of adult stem cells could generate all the types of tissues required to form complex mature lung. Regardless of whether others are able to reproduce this work, it is sure to generate interest because advances in the field of regenerating healthy lung tissue is something that could benefit millions of severely disabled patients.

This month’s literature continued to produce a yin and yang of good news and disappointment for reprogrammed cells. It saw one team directly reprogram skin tissue into functional liver cells and another produce a model of schizophrenia in a lab dish (See From stem cell to schizophrenia in a dish). That paper showed real differences between neurons grown from iPS cells made from normal individuals and those with the disease—and those differences could yield drug targets. But the literature also revealed that iPS cells could face immune rejection even when they are transplanted into an animal that is genetically matched. (See iPS cell smack down) We have to continuously tell ourselves that the iPS field is only five years old and these mixed results will get worked out and understood over time.

As we move closer to the clinic, we are increasingly concerned with efficiency of cell production and getting quantities of cells sufficient to run a clinical trial. This month saw papers greatly improving the efficiency of generating blood precursor cells from embryonic and induced stem cells and of generating neural precursor cells from embryonic stem cells.

Last, is a paper that offers some hope for my hair follicle challenged colleagues. Actively growing patches of hair appear to require some level of cross talk between hair stem cells. But this paper does have a more serous note. This same communication between stem cells may be critical in tissues like the intestine that have rapid cell turn over.

I hope you find the somewhat longer descriptions in my full report interesting.

On stem cells, sports injuries and aging

A headline today grabbed my attention: Can your own stem cells heal your running injuries?

The answer, in a word: Duh.

That's the whole point of tissue-specific stem cells like the ones lurking in muscles. These are the body's reservoir for repairing and rebuilding tissues. In fact, several CIRM grantees are studying what makes muscle stem cells tick, and what make them tick less effectively as we age. A bit of shameless self-promotion, but here's a story by yours truly from the Stanford School of Medicine magazine about work by Tom Rando, who was studying signals that direct muscle stem cells to heal injuries. His post-doctoral student Irina Conboy went on to found her own lab at the University of California, Berkeley, where she got a New Faculty Award to continue the work (we've blogged about her work here).

I suppose what's implied in the headline isn't whether stem cells normally heal injuries, which they do, but whether they can be used medically to heal injuries more effectively as in the case of the baseball pitcher Bartolo Colon.

To date, CIRM isn't funding work relating directly to, say, shin splints or plantar fasciatis. But a number of grantees are studying not only muscle stem cells but also another type of stem cell called a mesenchymal stem cell that seems to be able to repair bone and cartilage. (Here's a list of all CIRM awards targeting bone, muscle or cartilage.) What's exciting about a lot of the basic stem science going on today is that it could lead to new ways of treating a wide range of different injuries, either by injecting a person's own stem cells or by helping the native stem cells heal more effectively.

As a runner who is inevitably aging, I think it's good news that research into chronic, debilitating conditions such as osteoarthritis could also provide some benefit down the road to my own damaged joints.

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iPS cells reveal stem cell origin of disease

A new Nature paper from CIRM grantees at Stanford University once again shows the value of reprogrammed iPS cells in understanding disease. Scientists can't develop a therapy for a disease if they don't know what it is going wrong. In many cases, iPS cells have provided the first ever way of peering into diseased cells and finding which proteins and genes need fixing.

In this case, the disease in question is dyskeratosis congenita, in which the caps on the ends of chromosomes shorten abnormally and causes a wide variety of symptoms ranging from abnormal skin pigmentation and nail growth to lung scarring, bone marrow failure and cancer. The question has been why people with the same disease can have such dramatically different symptoms, and what to do about those symptoms.

The Stanford group reprogrammed the skin cells of people with the disease into embryonic-like iPS cells. They knew people with the disease made low levels of a protein conglomerate called telomerase, which is responsible for maintaining those chromosomal caps. What they found in those iPS cells is that the more severe a person's disease, the less telomerase their iPS cells made.

A Stanford press release quotes senior author Steven Artandi:

"We were very surprised to find such a clear correlation between the quantity of functional telomerase, the severity of the cellular defect and the severity of the patient's clinical symptoms," said associate professor of medicine Steven Artandi, MD, PhD. "Our work suggests that, in patients with dyskeratosis congenita, tissue stem cells are losing their ability to self-renew throughout the body. This is a new, unifying way to think about this disease, and it has important implications for many other conditions."

Reprogrammed iPS cells can normally divide indefinitely in the lab. The iPS cells made from people with dyskeratosis congenita eventually stopped being able to divide and instead matured into the body's cell types. The researchers think this means the disease symptoms occur when stem cells in the tissues lose their ability to divide indefinitely. With no stem cells in the bone marrow, skin or other organs, the person's body can't repair damage or maintain tissues. That seems to be what causes symptoms of dyskeratosis congenita.

Nature, May 22, 2011
CIRM funding: Steven Artandi (RB2-01497)

Gene replacement in stem cells made easier

A press release about CIRM grantees at the Salk Institute for Biological Studies contains what might be the truest words in stem cell science:

In principle, genetic engineering is simple, but in practice, replacing a faulty gene with a healthy copy is anything but.

Several CIRM grantees could sum up their work in that same way. We've funded a variety of projects that all intend to replace faulty genes in stem cells with healthy ones, and then use the tricked-up stem cells to treat disease. That's how both of our HIV/AIDS disease teams hope to conquer HIV infection and also underlies our sickle cell disease and epidermolysis bullosa teams. (A list of disease teams with links to their research summaries is available here.)

The Salk researchers have published a paper in Cell Stem Cell describing a new way of replacing a gene with a therapeutic version. As a model, they used stem cells they had reprogrammed from a person with a genetic premature aging condition called Hutchinson-Gilford progeria. That condition is caused by a mutation in a gene called Lamin A. They used the technique to replace the defective Lamin A in the reprogrammed stem cells with a healthy copy of the gene. According to postdoctoral researcher and co-first author Guang-Hui Liu:

"The process was remarkably efficient and we couldn't detect any undesired off-target effects such genomic instability or epigenetic abnormalities," says Liu. "What's more, it allowed us to show that we can correct multiple mutations spanning large genomic regions."

The group also showed that their technique worked in mesenchymal stem cells, which are a form of tissue-specific stem cells many groups are also using to develop therapies.

The issue of being able to swap out defective genes is just one of many hurdles for scientists developing stem cell-based therapies. These behind-the-scenes issues rarely make the newspapers and remain largely invisible to the people who are waiting to see those future therapies, but are an active area of research for CIRM grantees. Hopefully work like this will help eliminate those hurdles and speed the path to the clinic.

Cell Stem Cell, May 19, 2011
CIRM Funding: Jeanne Loring (TR1-01250), Guang-Hui Liu (TG2-01158)

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Funding students, fueling stem cell science

California State University Long Beach has a nice story today about their students funded by our Bridges to Stem Cell Research program. Mostly, CIRM funds science. But in order for that science to move forward we also need to make sure the state has enough trained stem cell scientists. What's the point of fostering new labs and biotech companies without people who know how to handle the notoriously tricky cells?

Thus the Bridges program. We first funded the undergraduate and masters programs back in January 2009 (here's our press release about the funding). Each of the 16 funded schools supports a handful of students who take classes and participate in research with collaborating institutions. As the first round of students complete their programs we're hearing back that the students are being hired in large numbers by the labs where they did their internships.

One of the students in the CSULB story, Colleen Worne, had this to say about her internship:

“The CIRM program will equip me with the skills and techniques necessary to succeed under such challenging conditions and achieve my career goals,” she continued. “From a young age I have pursued my passion for biology and research, knowing that helping society in a scientific capacity was, and is, my goal. CSULB has provided me with the scientific background for acceptance into the CIRM program. I am beyond excited to start my lifetime pursuit made possible by such an amazing program.”

We produced a video about Bridges students and California State University San Francisco last year. It's fun to see how excited the students are about pursuing stem cell science.



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Eradicate cancer stem cells, eradicate drug-resistant leukema

Markus Müschen/UCSF

CIRM grantees at the University of California San Francisco have found the protein certain leukemia cells use to evade chemotherapy. A press release from UCSF says:

Doctors who treat children with the most common form of childhood cancer – acute lymphoblastic leukemia – are often baffled at how bulk cancer cells die from chemotherapy whereas the rare stem cells in cancer survive their best efforts and the most powerful modern cancer drugs. Months after a seemingly successful treatment, the cancer stem cells re-initiate the disease, which is then more resistant to treatment than before.

It turns out the resistant cancer stem cells make a protein called BCL6, which protects them from the effects of chemotherapy. In a Nature paper published today, the team tested an experimental drug called RI-BPI, which attacks cells that make BCL6. Combined with the drug Gleevac, which is very effective at destroying the non-BCL6 cells, the experimental drug could effectively cure mice with drug resistant leukemia. In the release, CIRM grantee and senior author Markus Müschen said:

“We believe this discovery is of immediate relevance to patient care.”

In the work reported in this paper, the team used a molecule to block BCL6 that, though effective for small scale use, would be difficult to mass produce. Müschen has a CIRM Early Translational II Award to develop a drug that is similarly effective at destroying drug-resistant leukemia cells but that would be easier to mass produce for widespread use.

We have more information about cancer stem cells on our website:

• Leukemia information
• Cancer stem cell video

Nature, May 18, 2011
CIRM Funding: Markus Müschen (TR2-01816)

Clinical trial participation essential

Michael J. Fox has an excellent — and somewhat pointed — Op-Ed in today's San Francisco Chronicle in which he points out that if people want cures, they need to participate in research. He says:

Today, America is waiting expectantly for a new generation of scientific breakthroughs - in cancer, AIDS, Alzheimer's disease and, of course, Parkinson's disease. Yet we've lost sight of a critical element of any success - our own active engagement in the process.

He goes on to point out that 85 percent of clinical trials finish late because of trouble recruiting volunteers and nearly a third of all trials fail to recruit any patients at all. Case in point, Stem Cells Inc recently had to cancel their neural stem cell trial for the fatal childhood disorder Batten disease because they failed to recruit patients.

Fox goes on to say:

We're doing everything we can to identify and dismantle roadblocks that stand in the way of research progress. So far we've invested more than $230 million in research to speed new and better treatments for the disease. But we've been aware for years that dollars alone won't solve this problem. In particular, money cannot buy the critical contributions made by clinical trial volunteers.

At CIRM, that number is $1.2 billion, but the sentiment is the same. The only way research we fund can eventually become widely available therapies is through clinical trials that prove that the approach is safe and effective.

CIRM just started funding clinical trials, with a $25 million loan to Geron. We have 14 Disease Teams which are working toward clinical trials that they hope to start in 2013, and we have a new wave of Disease Teams coming down the pipeline. We look forward to working with patient advocacy groups to make sure those future trials are successful. In the mean time, if you or a loved one wants to participate in a clinical trial an excellent resource for finding those trials is the NIH clinical trials database: clincaltrials.gov.

A.A.

From the just plain cool files

I'm thrilled to have a legitimate reason to blog about the lowly planeria. This little flat worm is renowned amongst high school and freshman biology students for it's ability to regrow copies of itself when cut in half. In theory, slicing right between the planeria's eyes can even produce a two-headed worm, though that's one of the many experiments that never actually worked for me.

It turns out that what allows planeria to regenerate could also teach scientists about our own regenerative stem cells. Two papers in last week's Science investigated the planeria's regenerative stem cells, called neoblasts. They found that at least some of the neoblasts have the ability to form all tissues in the worm's body, much like embryonic stem cells or reprogrammed iPS cells.

A press release from the Whitehead Institute quotes one of the co-first authors Dan Wagner:

“This is an animal that, through evolution, has already solved the regeneration problem,” says Wagner. “We’re studying planarians to see how their regeneration process works. And, one day, we’ll examine what are the key differences between what’s possible in this animal and what’s possible in a mouse or a person.”

The team also identified some of the signals that tell the neoblast whether it should form a head or a tail. This polarity issue is a big deal. A stem cell that can become anything needs clues to tell it what to and not to become. That's as true in a human as it is in a worm.

A. A.

iPS cell smack down

Pity the iPS cell -- it's had quite a ride this year. On the upside, cells reprogrammed from people with autism, Parkinson's disease and schizophrenia were used to create the first ever models of those diseases in a dish. Those models could provide a way of testing drugs on actual human cells. That's good.

But in the same year, a number of studies found significant genetic differences between reprogrammed iPS cells and their embryonic counterparts (here's our blog entry). Today, a paper published in Nature by CIRM grantee Yang Xu at the University of California, San Diego found that the cells can also be rejected by the body.

This finding is a bit of a blow. When Shinya Yamanaka and colleagues first reprogrammed human skin to an embryonic-like state in 2007 the stem cell world was aflutter. These cells were seen by some as a possible replacement for embryonic stem cells, with the advantage that because they could be generated from a person's own skin they would be genetically identical and not get rejected by the immune system.

It turns out the immune system is smarter than that, at least in mice. The mice were able to detect and subsequently reject genetically identical iPS cells.

A New York Times story quotes George Daley of Boston Children's Hospital:

“As with any new technology, there is always this initial phase of infatuation, and then the reality sets in,” said Dr. George Q. Daley, director of the stem cell transplantation program at Children’s Hospital Boston. “I think it goes to the heart of the issue of how ignorant we really are in understanding these cells.”

Apparently what made the cells visible to the immune system were the genes that were activated in order to reprogram the cells. The immune reaction varied depending on how the cells were made. This work isn't exactly the death knell for iPS cells, but it does mean that the path to the clinic could be a tricky one.

May 13, Nature
CIRM Funding: Yang Xu (TR1-01277)

A.A.

Lung stem cell found, controversy ensues

Scientists at Brigham and Women's Hospital in Boston have reported that they identified a stem cell in lung. The work was published in the May 12 issue of the New England Journal of Medicine.

In the popular press you often read that adult stem cells exist in all the tissues of the body. This is likely true, but the reality is that scientists have only identified stem cells in a handful of tissues. They think all or most tissues contain a reservoir of restorative stem cells, but can't necessarily put their finger on them. And cells you can't identify are cells you can't turn into therapies or use to study disease.

Now that the team has isolated these potential lung stem cells, they can start thinking about using them. An Associated Press story quotes the study's authors Piero Anversa and Joseph Loscalzo:

Loscalzo said it's too early to tell what lung diseases might be treated someday by using the cells. He said researchers are initially looking at emphysema and high blood pressure in the arteries of the lungs, called pulmonary hypertension. Emphysema is a progressive disease that destroys key parts of the lung, leaving large cavities that interfere with the lung's function.

Anversa said the cells may also prove useful to build up lungs after lung cancer surgery. It's not clear whether they could be used in treating asthma, he said.

While a lung stem cell theoretically could be used to grow a lung in a lab for transplant, Loscalzo said that would be very difficult because the lung is so complex. Instead, he said, scientists will first look at isolating the cells from a patient, multiplying them in the laboratory, and then injecting them back into the patient's lung.

Nature has a blog entry on this paper in which they point out that Anversa has made controversial claims about stem cells in the past, including a 2001 paper in which he claimed bone marrow stem cells could turn into heart muscle in mice, work that Stanford's Irv Weissman said he couldn't replicate.

Nature quotes Amy Wagers, one-time post-doctoral researcher with Weissman and now scientific neighbor of Anversa's. Wagers works at the Joslin Diabetes Center, also affiliated with Harvard:

When I began my position as a postdoctoral fellow in Irv Weissman's lab at Stanford, there was a lot of enthusiasm surrounding the idea that hematopoietic stem cells in the bone marrow might spontaneously transdifferentiate to produce non-blood tissues. I rigorously tested this idea and found such activity to be negligible, if present at all. That changed the course of investigation by shifting the emphasis towards defining endogenous tissue progenitor cells that carry out regenerative functions.

All this just goes to show that grand pronouncements (or perhaps just simplified pronouncements) in the press don't always tell the full story about the science. Time will tell whether the lung stem cells announce today will turn out to be therapeutically useful, and in what way.

A.A.

Funding collaborations to find new therapies

Back in October the CIRM Governing Board heard from Victoria Jackson, who, in addition to being a powerful businesswoman in the cosmetics world, founded the Guthy-Jackson Charitable Foundation to drive cures for the rare autoimmune disease NMO (neuromyolitis optica or Devic's disease), which her daughter Ali developed as a teenager.

Videos of those NMO talks are available here. I highly recommend listening to Jackson speak. She's smart, compassionate, and hysterical.

What was so inspiring about Jackson's talk was her fearlessness in changing the status quo in disease research. Few scientists were studying NMO, and those that were weren't talking to each other or to the scientists who worked on related topics. And when she pushed them to talk she was told that's not how science happens. But when you are Victoria Jackson and you have both a checkbook and a daughter with a rare, incurable disease, it turns out you can make collaboration be how science happens. She now has 11 advisors who help guide funding to eight research sites and three clinical sites.

For me, Jackson's talk really spoke to CIRM's mission of accelerating research. We're not in the business of throwing money at science and hoping one day cures might happen. People voted for Proposition 71 with the understanding that we'd we'd work tirelessly to make those cures happen. So, like the Guthy-Jackson Charitable Foundation and a few other organizations, CIRM has been devising innovative funding strategies that will push scientists to work together and get to cures faster. It won't be tomorrow, or even next year, but we're pretty sure we'll get there sooner than we would if we just let science take its course.

We recently put together a short video about the power of collaboration, drawing on Jackson's experience.



A.A.

German stem cell clinic shut down amidst safety concerns

On Sunday the UK Telegraph reported the closing of a stem cell clinic in Germany that has been the source of international concern. Last year, a clinic offering stem cell cures in Costa Rica was shut down by the country's health ministry.

In both cases, the concern came from claims that injected stem cells would cure a wide range of diseases, even though there is no proof that the cells will be effective. One child who received stem cell injections at the German clinic died last August, and a second child also had complications. His family is suing the clinic.


According to the Telegraph:

A Sunday Telegraph undercover reporter who suffers from multiple sclerosis and is confined to a wheelchair was told last week during a consultation at the XCell-Center that he could walk again.

According to XCell, about 25 British patients a month – including children with severe disabilities – are treated at its clinic in Düsseldorf and at another in nearby Cologne.

The treatment involves taking bone marrow from patients, harvesting stem cells from the bone marrow and then reinjecting those stem cells into other parts of the body, including the brain, the spine and the neck.

The U.S. and other countries regulate clinical trials and demand proof that the proposed treatment is going to be safe and effective before researchers are allowed to try the technique in human patients. That process is slow, but it's also what stands between people and possibly deadly and ineffective therapies. Countries without stringent regulatory controls are now playing host to clinics much like the one in Germany who offer the promise of cures without proof.

The international community has become so concerned about the risk of these clinics that the International Society for Stem Cell Research launched a website offering to investigate claims of stem cell clinics before people spend money to travel overseas (see A Closer Look at Stem Cell Treatments). CIRM also offers information about stem cell tourism on our website.

Last year, CIRM co-sponsored a public seminar in partnership with the ISSCR on the responsible path for delivering stem cell therapies to the clinic. The video of that stem cell tourism seminar is on our website.

Krista Conger at Stanford University School of Medicine recently wrote an excellent piece about stem cell tourism for their magazine, which begins:

On the surface it seems easy. Overseas stem cell “clinics” peddling unproven treatments to desperate and dying patients, charging tens of thousands of dollars for the privilege of being injected with mysterious concoctions of cells meant to cure almost every ailment: What’s not to hate?

She goes on to quote CIRM grantee Jeanne Loring of Scripps Research Institute who says desperate patients don't see it that way:

“When we report something good about stem cells, it gets picked up in the media, or in a blog that patients read,” says Jeanne Loring, PhD, director of the Center for Regenerative Medicine at the Scripps Research Institute in La Jolla, Calif. “It gives them more ammunition to say that the FDA is stupid for denying access to treatments that seem like they should work.”

Loring has been actively involved in educating people about the dangers of stem cell tourism, and participated in this video with CIRM:



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Celebrating National Cancer Research Month with a cancer stem cell round-up

In celebration of National Cancer Research Month, our colleagues at Sanford-Burnham Medical Research Institute have posted a series of blog entries about cancer research at their institute. The latest installment includes CIRM grantee Robert Wechsler-Reya, who moved to California from Duke University on a CIRM Research Leadership Award.

According to their blog:

Dr. Robert Wechsler-Reya, who directs the Tumor Development Program in Sanford-Burnham’s Cancer Center, has spent many years studying how “good” processes can also cause disease. He is particularly interested in how mechanisms that are normal in embryonic development can cause cancer when turned on in children and adults.

“We work on the relationship between development and cancer, particularly in the brain,” says Dr. Wechsler-Reya. “We’re interested in how normal stem cells and progenitor cells make decisions like when to divide, when to differentiate and what to differentiate into. We’re interested in how those decisions go wrong in cancer.”

To-date, CIRM has awarded more than $130 million to cancer research, including grantees working to understand the role of cancer stem cells in the disease and other teams working to develop therapies. Among our Disease Team projects, which have the goal of reaching clinical trials by 2014, CIRM funded two teams working on therapies for glioma (City of Hope and UCSF), two working on therapies for leukemia (Stanford and UCSD), and one working on solid tumors (UCLA).

Here are a few resources CIRM offers for people trying to get information about stem cells and cancer.

• Information about stem cells and glioma
• Information about stem cells and leukemia
• Information about stem cells and solid tumors

We also produced this video with CIRM grantee Catriona Jamieson at Moore's UCSD Cancer Center at the University of California, San Diego. Jamieson has a therapy in clinical trial for a pre-cancerous blood condition. The work that led to that trial was funded in part by a CIRM SEED grant.



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How a stem cell forms a neuron

CIRM grantees at Sanford-Burnham have published another paper using an embryonic stem cell model to understand one of the earliest steps in human nervous system development. (We've blogged about their work before here.)

The group led by Alexey Terskikh has been trying to understand how a group of cells called the neural crest form nerves, skin, bone and muscle. This process has been somewhat mysterious because it happens at such an early stage in development. Scientists can't exactly peer into a woman's womb to see the process unfold.

That's where embryonic stem cells come in. These cells can form all cell types in the body, including neural crest. On their blog, Sanford-Burnham quotes first author on the May 5 Cell Stem Cell study Flavio Cimadamore:

“Neural crest cells are notoriously difficult to study in humans because of their very early and transient nature – a woman is usually not even yet aware of her pregnancy when they start to migrate and differentiate. So here we took advantage of an embryonic stem cell-based model of human neural crest previously developed in our lab to get a better understanding of the molecular pathways that control the differentiation potential of such cells in humans.”

In the current work, the team found that neural crest cells with a gene called SOX2 turned on can go on to form neurons. Those without it can't. That's critical information for people who are trying to understand diseases that arise from neural crest cells that go awry during development. Microphthalmia and CHARGE syndrome are two rare but debilitating childhood diseases that could benefit from knowing more about how the neural crest normally develops.

In the blog entry, Terskikh said:

"We hope this finding will be useful to researchers studying neural crest development and stem cell differentiation.”

CIRM funding: Alexey Turskikh (RS1-004661); Flavio Cimadamore (TG2-01162)
Cell Stem Cell, May 5

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Guest blogger Roman Reed: spinal cord injury stem cell trials get $25 million boost from CIRM

From the editor: Yesterday the CIRM governing board approved a $25 million loan to help fund a trial testing the use of an embryonic stem cell-derived therapy for spinal cord injury. Here's our press release. Our guest blogger Roman Reed was injured in a football accident and has since fought tirelessly for spinal cord injury research.

Yesterday's announcement that CIRM will help fund the Geron spinal cord injury Human Trials ensures that paralysis cure will have it's day!

It was my honor to be the inspiration of the Roman Reed Spinal Cord Injury Research Act in 1999, which provided the original funding for Hans Keirstead's research which is being tested in these trials, the first in the world.

However, the expense of the trials might conceivably have exhausted Geron's financial resources, narrowing the scope of the trials. This would have been devastating, not only to our hopes for paralysis cure but also for the entire field. The world is watching. Had the trials been too limited for lack of funding, it might have cast a shadow of doubt on its outcome-- instead, the trials go forward, strongly.

Geron's nine year struggle to build a mountain of preliminary data (so the FDA could approve the human trials) was an heroic effort, on which so much depended. With the leadership of Geron, the courageous biomed company came through for California and our country, and the world-- and so did the California stem cell program.

When the oversight committee announced its decision yesterday, it authorized a $25 million dollar loan to Geron to assist in the clinical trials. This was a careful loan, milestone driven, with each installment given only on the successful completion of predetermined goals.

I join the patient advocate community across the globe in expressing absolute full support of CIRM's descision to provide funding for America's first hESC derived Human Clinical Trials.

As a Patient and Patient advocate, I am overjoyed that Prop.71 took a stand for the Geron trials, the most important experiment in the world for the fields of spinal cord injury, neuro-regenerative medicine and stem cell research.

Truly, the Geron Trials are setting the pace of spinal cord injury. Paralysis affects 650,000 Californians and 1.9 million Americans, with an additional 5.6 million Americans who suffer from all forms of paralysis. (Here's information about CIRM's funding for spinal cord injury stem cell research.)

This epic step was accomplished through partnership and collaboration through a new age continum of support beginning with State funding from Roman Reed Spinal Cord Injury Research Act, Education at the University of California, Irvine, private industry support from Geron and voter-approved CIRM/State funds.

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 vote of support is a truly historic milestone in medicine.

Ladies and Gentlemen welcome to the beginning of personalized stem cell medicine and cure!

Thank you Prop.71 for Taking A Stand-- So One Day-Everybody Can!

Here's Roman Reed discussing stem cell-based therapies for spinal cord injury: