Stem cell stories that caught our eye: a new type of stem cell, stomach cancer and babies—stem cell assisted and gene altered

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.

New type of stem cell easier to grow, more versatile. Both the professional scientific media and the lay science media devoted considerable ink and electrons this week to the announcement of a new type of stem cell—and not just any stem cell, a pluripotent one, so it is capable of making all our tissues. On first blush it appears to be easier to grow in the lab, possibly safer to use clinically, and potentially able to generate whole replacement organs.

The newly found stem cells (shown in green) integrating into a mouse embryo.

The newly found stem cells (shown in green) integrating into a mouse embryo.

How a team at the Salk Institute made the discovery was perhaps best described in the institute’s press release picked up by HealthCanal. They sought to isolate stem cells from a developing embryo after the embryo had started to organize itself spatially into compartments that would later become different parts of the body. By doing this they found a type of stem cell that was on the cusp of maturing into specific tissue, but was still pluripotent. Using various genetic markers they verified that these new cells are indeed different from embryonic stem cells isolated at a particular time in development.

The Scientist did the best job of explaining why these cells might be better for research and why they might be safer clinically. They used outside experts, including Harvard stem cell guru George Daly and CIRM-grantee from the University of California, Davis, Paul Knoepfler, to explain why. Paul described the cells this way:

“[They] fit nicely into a broader concept that there are going to be ‘intermediate state’ stem cells that don’t fit so easily into binary, black-and-white ways of classifying [pluripotent cells].”

The Verge did the best job of describing the most far-reaching potential of the new cells. Unlike earlier types of human pluripotent cells, these human stem cells, when transplanted into a mouse embryo could differentiate into all three layers of tissue that give rise to the developing embryo. This ability to perform the full pluripotent repertoire in another species—creating so called chimeras—raises the possibility of growing full human replacement organs in animals, such as pigs. The publication quotes CIRM science officer Uta Grieshammer explaining the history of the work in the field that lead up to this latest finding.

Stem cells boost success in in vitro fertilization.  Veteran stem cell reporter and book author Alice Park wrote about a breakthrough in Time this week that could make it much easier for older women to become pregnant using in vitro fertilization. The new technique uses the premise that one reason older women’s eggs seem less likely to produce a viable embryo is they are tired—the mitochondria, the tiny organs that provide power to cells, just don’t have it in them to get the job done.

The first baby was born with the assistance of the new procedure in Canada last month. The process takes a small sample of the mother-to-be’s ovarian tissue, isolates egg stem cells from it, extracts the mitochondria from those immature cells and then injects them into the woman’s mature, but tired eggs. Park reports that eight women are currently pregnant using the technique. She quotes the president of the American Society of Reproductive Medicine on the potential of the procedure:

“We could be on the cusp of something incredibly important. Something that is really going to pan out to be revolutionary.”

But being the good reporter that she is, Park also quotes experts that note no one has done comparison studies to see if the process really is more successful than other techniques.

Why bug linked to ulcers may cause cancer. The discovery of the link between the bacteria H. pylori and stomach ulcers is one of my favorite tales of the scientific process. When Australian scientists Barry Marshall and Robin Warren first proposed the link in the early 1980s no one believed them. It took Marshall intentionally swallowing a batch of the bacteria, getting ulcers, treating the infection, and the ulcers resolving, before the skeptics let up. They went on to win the Nobel Prize in 1995 and an entire subsequent generation of surgeons no longer learned a standard procedure used for decades to repair stomach ulcers.

In the decades since, research has produced hints that undiagnosed H. pylori infection may also be linked to stomach cancer, but no one knew why. Now, a team at Stanford has fingered a likely path from bacteria to cancer. It turns out the bacteria interacts directly with stomach stem cells, causing them to divide more rapidly than normal.

They found this latest link through another interesting turn of scientific process. They did not feel like they could ethically take samples from healthy individuals’ stomachs, so they used tissue discarded after gastric bypass surgeries performed to treat obesity. In those samples they found that H. pylori clustered at the bottom of tiny glands where stomach stem cells reside. In samples positive for the bacteria, the stem cells were activated and dividing abnormally. HealthCanal picked up the university’s press release on the work.

Rational balanced discussion on gene-edited babies.   Wired produced the most thoughtful piece I have read on the controversy over creating gene-edited babies since the ruckus erupted April 18 when a group of Chinese scientists published a report that they had edited the genes of human eggs. Nick Stockton wrote about the diversity of opinion in the scientific community, but most importantly, about the fact this is not imminent. A lot of lab work lies between now and the ability to create designer babies. Here is one particular well-written caveat:

“Figuring out the efficacy and safety of embryonic gene editing means years and years of research. Boring research. Lab-coated shoulders hunched over petri dishes full of zebrafish DNA. Graduate students staring at chromatographs until their eyes ache.”

He discusses the fears of genetic errors and the opportunity to layer today’s existing inequality with a topping of genetic elitism. But he also discusses the potential to cure horrible genetic diseases and the possibility that all those strained graduate student eyes might bring down the cost to where the genetic fixes might be available to everyone, not just the well heeled.

The piece is worth the read. As he says in his closing paragraph, “be afraid, be hopeful, and above all be educated.”

New Video: Defeating Sickle Cell Disease with Stem Cells + Gene Therapy

Suffering with an incurable illness is no laughing matter. But last year when we debuted the pilot episode of Stem Cells in Your Face, a lighthearted video series that describes specific diseases and explains the latest progress in stem cell-based therapies, we hoped that a mix of science and humor would help make the information stick in the minds of our viewers. We were thrilled, based on your comments, that you enjoyed watching Treating ALS with a Disease in a Dish as much as we enjoyed producing it and that you wanted to see more:

“Very informative yet easy to understand pilot episode! Hope to see more in this series soon!”

“Might I suggest highlighting a different disease CIRM focuses on in each video?”

Ask and you shall receive. This week we’ve posted the second installment: Defeating Sickle Cell Disease with Stem Cells + Jean Gene Therapy which is being rolled out as a companion piece to our new blog feature series, Genes + Cells.

The video highlights a CIRM-funded clinical trial at UCLA that is testing a stem cell and gene therapy treatment for sickle cell disease. This awful genetic disorder causes red blood cells to assume a sickle shape, clogging blood vessels and producing episodes of excruciating pain, called crises, and leading to progressive organ damage. By twenty years of age about 15 percent of people with sickle cell disease have had major strokes and by 40 almost half of the patients have significant mental dysfunction. The disease strikes one in 500 African Americans and 1 in 36,000 Hispanic people.

A standard treatment for sickle cell disease is a blood transfusion but the benefits are short-lived and require repeated procedures. Bone marrow transplants can be curative but they require a well-matched blood donor which is hard to find and can still be very risky. The UCLA team, on the other hand, aims to correct the sickle cell genetic mutation within the blood stem cells of the patient, which in theory could provide a life-long supply of normal shaped red blood cells. Don Kohn, the lead scientist on the team, explains their strategy in the video:

“The approach that we’re looking at would be to take the patient’s own bone marrow, isolate the [blood] stem cells, in the laboratory put in the gene we’ve been working on that prevents the red blood cells from sickling. So transplanting their own bone marrow back to them in theory should be safe, we don’t have to worry about rejection.“

If all goes well, sickle cell disease may soon be a thing of the past. As patient advocate Adrienne Shapiro has so eloquently stated in a previous Stories of Hope blog post:

“It’s my true belief that I’m going to be the last woman in my family to have a child with sickle cell disease. My afflicted daughter is going to be the last child to suffer, and my other daughter [who does not have the disease but carries the sickle cell mutation] is going to be the last one to fear [passing on the disease to her children]. Stem cells are going to fix this for us and many other families.”

This clinical trial represents one of the first trials to be part of CIRM’s Alpha Stem Cell Network. To learn more, visit our Alpha Clinic webpage. And for more details about CIRM-funding of sickle cell disease research visit these pages:

Genes + Cells: Stem Cells deliver genes as “drugs” & hope for ALS

This month a lab animal will become the initial patient in the final steps in Clive Svendsen’s 15-year quest to provide the first meaningful therapy for people with ALS, also known as Lou Gehrig’s disease. If that animal and subsequent ones in this required study have good results—no side effects from the treatment—Svendsen plans to take that data to the Food and Drug Administration in November to seek approval to begin a human clinical trial.

Clive Svendsen has been on a 15-year quest to develop an ALS therapy

Clive Svendsen has been on a 15-year quest to develop an ALS therapy

A native of England, Svendsen first started trying to merge gene therapy and stem cell therapy at Cambridge working with Parkinson’s disease. But after moving to the University of Wisconsin in 2000 and being approached by the ALS Association he switched to ALS. He has continued the work since moving to Cedars-Sinai in Los Angeles in 2010 where he receives CIRM funds to do the necessary animal tests as well as for the first human trial.

By contrast, Nanci Ryder’s voyage with ALS has only been a few short months. Since being diagnosed with the disease in August 2014 she has thrown herself into learning about it. “The only power I have ever felt over the adversity of a life threatening disease is knowledge.” She has also enlisted the help of many of the celebrity actor-clients of her public relations firm to advocate for ALS research funding, even though she knows the research may not move fast enough to help her.

A previous ALS stem cell trial shows the ups and downs faced by advocates for this stubborn fast-progressing and ultimately fatal disease. Largely conducted at the University of Michigan and Emory University that trial had provided one of the early hints of success with a potential stem cell therapy. But a subsequent larger trial did not achieve the results it was hoped it would produce.

Svendsen argues that trial has provided valuable insights, proven that you can put stem cells in the spinal cord and provides some rational as to why his team may have greater success. The Cedars team uses a different type of cell and boosts those cells’ performance with an added copy of a gene that makes a protein known to protect the type of nerves destroyed in ALS.

The earlier trial used cells from the spinal cord; Svendsen’s team uses cells from the brain’s cortex. In both cases the cells were recovered from discarded fetal tissue, but the cells from the cortex migrate better after transplantation and are more likely to spread out and have an impact on a greater area. Both teams transplant middleman cells that are part way down the path between stem cells and mature adult cells. But those stem/progenitor cells from the two teams mature into different adult nerve tissue. The ones from the spinal cord mostly become nerve cells called interneurons, while those from the cortex being used at Cedars all transform into astrocytes, the cells that protect nerves. Astrocytes have been shown to go bad in ALS and it is their malfunction that puts the body on a deadly path to paralysis.

In addition to potentially replacing the nerves’ valuable damaged support cells Svendsen hopes to boost the chances for therapeutic success by making the cells a drug delivery vehicle. The drug of choice: a growth factor called GDNF known to enhance the survival of many types of nerves. Both of the cell types used in ALS so far produce small quantities of GDNF, but the Cedars team wants to crank up that production.

That’s where the gene therapy comes into play. The Cedars team uses a modified lentivirus as a delivery vehicle to carry the GDNF gene into the stem cells. They have shown that half of the stem cells end up having copies of the gene and make the protective elixir. Once transplanted, the cells continue to pump out GDNF into the damaged area—helping the patient’s own neurons survive and function.

As Svendsen and his colleagues complete the last tests needed to get permission to test their one-two-punch cells in humans, they are already working on a key refinement. They would like to be able to regulate when and for how long the therapeutic gene is turned on—to actually make the protective protein on demand. This could be key if any side effects develop. Using a trick that other gene therapy experts have used, they plan to further modify the genetic manipulation so that the gene is only turned on in the presence of the antibiotic doxycycline. So, taking a pill could activate the gene.

After 15 years of intense effort, you can hear the excitement in Svendsen’s voice when he talks about the possibility of beginning a clinical trial later this year. He has all the additional processes in place and says, “we will begin recruiting patients the first week we have approval.”

[May is ALS Awareness month if you want to find out more about how you can help fight the disease visit the ALS Goldenwest chapter website]

Thrust into ALS Advocacy

A publicist for big-name stars, Nanci Ryder found herself thrust into ALS advocacy after her diagnosis last summer.

A publicist for big-name stars, Nanci Ryder found herself thrust into ALS advocacy after her diagnosis last summer.

I have always had a fascination for medicine, and thanks to the Internet, I’ve become a tireless researcher. Having already faced breast cancer a decade ago, the only power I have ever felt over the adversity of a life-threatening illness is knowledge. When I was diagnosed in August 2014 with bulbar ALS, I had to know the specifics of the disease. But more importantly, I had to know who was at the forefront fighting it.

Having spent my entire professional career providing public relations counsel to hundreds of actors and entertainers, I was no stranger to the value of their influence in bringing attention to far-ranging issues, and ALS would be no exception. I had seen what my longtime client Michael J. Fox was able to do for Parkinson’s research and I was determined to follow his example. With the support of clients past and present, Renee Zellweger, Reese Witherspoon, Emmy Rossum and many others, I immediately decided I would commit my energies to support awareness efforts that would translate into additional funding for research.

I met Clive Svendsen through the Cedar Sinai ALS program. I had read about his research in gene therapy and later toured his lab with my friend and ALS advocate, Courteney Cox. We were both very excited by the promise of his research. While there are no cures, I was admittedly daunted when I discovered I was not a candidate for any of the gene therapy clinical trials since my ALS (bulbar) began in the brain, and not in the spine as in 99% of cases.

We cannot always derive the benefits of our efforts for ourselves, but we can help others. That is my life’s path.

Nanci Ryder

Genes + Cells: Stem Cells Deliver Genetic Punch

Bad luck stalked the early years of gene therapy. The pioneering research revealed it is difficult to manipulate a patient’s genes both efficiently and safely. Today, after more than two decades of tireless labor in the lab, nearly 2,000 gene therapy trials have been conducted or are approved, with many of the most promising using stem cells to carry the genetic tricks.

CIRM is providing $110 million in funds for nine projects that have made it into the clinic—or hope to get there soon—by marrying the power of gene manipulation and stem cells. We have several other projects combing the two therapy tools in earlier stages of development.

The first gene therapy trial in the U.S. in 1990 sought to cure Severe Combined Immune Deficiency (SCID), or ‘bubble-baby disease,” and produced modest success. But it did not last. The gene-modified cells did not stick around. Much tinkering ensued to create better ways of getting the desired therapeutic gene into cells, but one of those new tools resulted in the death of a patient in a clinical trial in 1999. That death of Jesse Gelsinger led the Food and Drug Administration to suspend several ongoing clinical trials. Then the 2003 death of a SCID patient from leukemia, believed to have been caused by another gene delivery approach, further dampened the field.

But researchers who see great potential for treating unmet medical needs are not easily dissuaded. The pioneers of gene therapy studied why the deaths occurred and found gene delivery tools that would not go down those same unsafe paths. They discovered ways to get the genes expressed by cells efficiently and longterm. CIRM grantee at the University of California, Los Angeles (UCLA), Don Kohn was helping lead the charge in the early days; despite setbacks he stuck with it, and last year announced that 18 kids had been cured of SCID using stem cells modified to produce the protein missing in the disease. He has just launched a clinical trial hoping to vanquish sickle cell anemia in the same way.

CIRM clinical projects combining stem cells and gene manipulation fall into three categories:

    1. Genetic fix when someone is born with a mutated copy of a gene.
    2. Gene modification to alter stem cells to give them a desired trait.
    3. Gene insertion as drug delivery to give cells a boost of a naturally occurring protein.

Both of the CIRM genetic fix projects seek to rectify errors in the gene for hemoglobin, the protein that our red blood cells use to carry oxygen. Kohn explains his work to provide a working copy of a hemoglobin gene in sickle cell patient’s blood-forming stem cells in our “Stem Cells in Your Face” video series.

Sangamo’s clinical trial won’t be correcting the defective hemoglobin gene in Beta Thalassemia patients directly, but instead will edit the patient’s genes to turn on the gene for fetal hemoglobin that is not normally active as an adult. The company’s team has shown that this gene can produce enough of the protein to end the patients’ need for constant blood transfusions, which up until now has been the only way for them to get healthy red blood cells.

Genetically modifying stem cells to give them desired traits comes in many forms. The two HIV/AIDS projects both seek to alter patients’ blood-forming stem cells so that they produce T cells that are immune to infection by the virus. City of Hope scientists, working with Sangamo, devised a way to alter a protein on the surface of T cells, called a receptor that the virus uses like a door to gain entry into the cells. It is like taking away the key so the virus can’t get in. The Calimmune team doubled down on door security. They are altering two different receptors the virus uses for entry.

Both of the cancer projects seek to alter blood-forming stem cells so that they produce immune system cells that are better targeted to killing a patient’s specific tumor.

Gene insertion to act as a “drug” delivery system also has diverse applications. The Huntington’s disease project uses a type of stem cell found in bone marrow called a mesenchymal stem cell (MSC) to deliver a nerve growth factor that has been shown to be protective of nerves facing the type of damage seen in Huntington’s.

The ALS project starts with cells called neural progenitors, “teenaged” cells that are only part way along the path of maturity between a nerve stem cell and the final adult brain cells. Once transplanted the cells should have a two-pronged benefit. They mature specifically into astrocytes, the initial brain cell to go bad in ALS, and the added gene will produce a growth factor that has been shown to be protective of the damage seen in ALS—a different growth factor than the one used in the Huntington’s research.

In limb ischemia, poor blood circulation and severe pain results from clogged blood vessels, so therapies that stimulate growth of new vessels make sense. A growth factor called VEGF has long been known to do this, but when doctors tried injecting it into aching legs it didn’t stick around long enough to do any good. MSCs are also known to stimulate blood vessel growth and have shown some benefit when transplanted into patients with limb ischemia. If that benefit could be ratcheted up patients could gain significant pain relief. The UC Davis team hopes to transplant MSCs that have an extra copy of the VEGF gene so they stimulate vessel growth through two paths.

The marriage of gene therapy and stem cell therapy seems likely to produce a number of live-happily-ever-after therapies.

Using stem cells to mend a broken heart and winning $6,000 to boot

It’s no secret that the members of the CIRM blog team are all big fans of scientists who are good public communicators. We feel that the more scientists talk about their research, the better the public will understand the importance of science and it’s ability to help them or someone they love.

Grad Slam winner, Ashley Fong from UC Irvine

Grad Slam winner, Ashley Fong from UC Irvine

So on Monday when University of California, Irvine researcher Ashley Fong won the $6,000 top prize in the Grad Slam competition for the terrific explanation of her work in using stem cells to treat heart disease, it was doubly gratifying. You see, not only is Ashley a great communicator, but she’s also someone we have helped support in her career.

The Grad Slam is an “elevator pitch” competition sponsored by the University of California Office of the President. Ten graduate students from across the UC system were given three minutes to explain their work to a live audience, using everyday language and avoiding jargon or technical lingo.

All the students were good. Ashley was great. Want proof? Here you go (Ashley comes on at 39.20 into the video.)

She says she discovered her passion for stem cell research thanks to a CIRM-funded summer undergraduate internship. Now she is working in the lab of Chris Hughes at UCI.

In a UCI News story about the competition Frances Leslie, dean of the Graduate Division who hosted the campus-level competition in April, said:

“It’s important for graduate students to explain their research to the general public in ways that are easy to understand. And it’s also critical for the taxpayers of California to see the benefits of their support of graduate education.”

We couldn’t have put it any better.

Stem cell stories that caught our eye: spina bifida, review of heart clinical trials, tracking cells and cell switches

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.

Stem cells boost fetal surgery for spina bifida. Fetal surgery to correct the spinal defect that causes spina bifida has revolutionized treatment for the debilitating birth defect in the past few years. But for one of the researchers who pioneered the surgery it was only a half fulfilled hope. While the surgery let most of the treated kids grow up without cognitive deficits it did not improve their ability to walk.

spina_bifida-webNow that researcher, Diana Farmer at the University of California, Davis, has found a way to complete the job. Though it has only been used in an animal model so far, she found that when you engineer a stem cell patch that you insert into the gap before you push the protruding spinal cord back in its place during surgery, the animals are able to walk within a few hours of birth.

Specifically, she used a type of stem cell found in the placenta that has been shown to protect nerves. She incased those cells in a gel and placed them on a scaffold to hold them in place after transplant. All six lambs that had surgery plus the cell transplant walked. None of the ones who just had surgery did.

“Fetal surgery provided hope that most children with spina bifida would be able to live without (brain) shunts,” Farmer said. “Now, we need to complete that process and find out if they can also live without wheelchairs.”

CIRM awarded Farmer’s team funds in March to carry this work forward and prepare it for a possible clinical trial. The animal study appeared in Stem Cells Translational Medicine this week and the university’s press release was picked up by HealthCanal.

Thorough, digestible review of heart trials. Kerry Grens, writing in The Scientist, has produced the most complete and understandable review of the clinical trials using stem cells to treat heart disease that I have read. More important she provides significant detail about the three large Phase 3 trials that are ongoing that could provide make-or-break outcomes for using bone marrow stem cells for patients developing heart failure.

The bulk of the piece focuses on research using various types of mesenchymal stem cells found in bone marrow. All three of the late stage clinical trials use those cells, two use cells from the patient’s own marrow and one uses cells from donors. Grens uses a broad spectrum of the research community describe what we currently know about how those cells may work and more importantly, what we don’t know. The experts provide a good point-counter-point on why there are so many clinical trials when we don’t really know those stem cells’ “method of action,” why they might make someone’s heart stronger.

However she leads and ends with work CIRM funds at Cedars-Sinai and Capricor Therapeutics in Los Angeles. That work uses cells derived from the heart called cardiosphere-derived cells. Early trials suggested these cells might be better at reducing scar tissue and triggering regrowth of heart muscle. Those cells are currently being tested in a Phase 2 study to try to get a better handle on exactly what their benefit might be.

Monitoring stem cells after transplants. Early attempts to use stem cells as therapies have been hampered by an inability to see where the cells go after transplant and if they stay the desired location and function. A team at Stanford has used some ingenious new technologies to get over this hurdle, at least in laboratory animals.

Using a homegrown technology that recently won a major innovation prize for a Stanford colleague, optogenetics, the team was able to selectively activate the transplanted cells. Then they used the older technology, functional Magnetic Resonance Imaging (fMRI), to see if the cells were working. Because cell transplants in the brain have led to some of the most difficult to interpret results in humans, they chose to work with nerve stem cells transplanted into the brains of rats. The work was partially funded by CIRM.

Starting with iPS type stem cells made from Parkinson’s patients’ skin, they inserted a gene for a protein that is sensitive to certain wavelengths of light. They then matured those cells into nerve stem cells and implanted them along with a tube that could transmit the right wavelength of light. Over the course of many months they measured the activity of the cells via fMRI with and without the light stimulation. Because the fMRI measures blood flow it by default detects active nerve cells that require more nutrients from blood than inactive cells. Senior researcher, Jin Hyung Lee described the value of this imaging in the university’s press release picked up by HealthCanal:

“If we can watch the new cells’ behaviors for weeks and months after we’ve transplanted them, we can learn — much more quickly and in a guided way rather than a trial-and-error fashion — what kind of cells to put in, exactly where to put them, and how.”

Understanding cell’s switchboard may speed therapy. Cells function by switching genes on and off. Learning which switches to hit to maximize stem cells’ ability to multiply and mature into desired cell types has occupied a significant part of the stem cell research community for years. Now, a team at the Salk Institute has shown that two known genetic switches pack an additive punch when working together.

Both those signaling processes, one called Wnt and one called Activin, are needed for stem cells to mature into specific adult tissue. The Salk team led by Kathy Jones found that when working together the two signals activate some 200 genes. Wnt seems to load the cellular equipment needed for copying the cells and Activin increases the speed and efficiency of the process. In an institute press release picked up by Science Newsline, Jones discussed the practical implications of the finding:

“Now we understand stem cell differentiation at a much finer level by seeing how these cellular signals transmit their effects in the cells. Understanding these details is important for developing more robust stem cell protocols and optimizing the efficiency of stem cell therapies.”

Charting a new, faster way to fund science and help patients

Change is never easy. In fact, sometimes it can be downright hard. But change is also essential if you want to grow, to get faster and better.

When we launched CIRM 2.0 we set out to produce a better, faster, more effective and efficient way to deliver stem cell therapies to patients with unmet medical needs. Yesterday we got a chance to see how those changes are starting to play out. And it was very encouraging.

Our Grants Working Group (GWG – we love our acronyms at CIRM. See!) is the independent panel of experts that we bring in to review all the applications for agency funding. They come from all over the US, except California, and Monday was the first chance they got to meet in person and vote on our new 2.0 applications.

The day began with a really in-depth look at how 2.0 works and how it differs quite dramatically from the old system. One of the things that always impresses me about the GWG is the extraordinary quality of the questions they ask and the level of detail they want to help them make the best possible decisions. While we would never divulge any applicant’s confidential or proprietary information, we were able to hold much of the meeting in open session – furthering our commitment to transparency.

I think Sen. Art Torres, the Vice Chair and a Patient Advocate member of our governing Board, summed it up best in a note that he sent to the CIRM Team following the meeting:

“Yesterday was a historic day for CIRM.  It was one of the best meetings I have attended and gave me renewed confidence in speaking to the public of how we continue to be responsible stewards of the taxpayers’ dollars while at the same time keeping patients as our number one priority.

I cannot speak for all the patient advocates but I think they were all impressed with the candor and meaningful dialogue that took place.

It also gave the GWG members time to bond in a very welcoming setting to express their ideas and their commitments.  I do not recall ever having a session with GWG members where they shared their personal views other than their reviews of a proposed grant.  It was revealing about how we can work more closely together with our common bonds.”

The results of the review of the first two applications under CIRM 2.0 will go to the Board for a vote on May 21, but the more important outcome will be the long-term benefit to the way we work. The in-person meeting helped the members of the GWG really understand how the changes to the way they work will speed up our ability to fund the most promising science.

This is all new, so it’s likely we’ll hit some bumps along the way. And as we roll out our new versions of 2.0 that cover funding Discovery (or basic) and Translational research later this year we’ll probably have more adjustments to make. You can’t change this much this fast and not run into problems.

But as the meeting yesterday showed so clearly, with the right team behind you even the biggest changes can be taken in stride.

Pioneering treatments: planning first-in-human stem cell clinical trials

Sometimes the reason for the most complex of projects can be boiled down to the most simple of phrases.

Dr. John Adams, Dr. Catriona Jamieson & Dr. John Zaia at the Alpha Stem Cell Clinic network meeting

(left to right) Dr. John Adams, Dr. Catriona Jamieson & Dr. John Zaia at the Alpha Stem Cell Clinic network meeting

At a meeting last week to help plan for our Alpha Stem Cell Clinic network there were lots of great presentations and discussions about the role of the network, how to structure it, what its goals would be. But in the end it was all beautifully, and succinctly, summed up by Dr. Catriona Jamieson who said: “This is great for humanity and this is why we have to do it.”

Dr. Jamieson is heading the University of California, San Diego (UCSD) part of the network. Other partners in this program are City of Hope, UC Los Angeles (UCLA) and UC Irvine (UCI). The goal is to create a network of stem cell-focused clinics that will attract and conduct high quality clinical trials. The stem cell agency is investing $24 million to help create that network.

Why do we need this? Well, stem cells are a whole new way of treating disease, one that requires new skills and expertise, and a new way of working with patients so they understand exactly what is happening.

Many of these clinical trials will be the first time these therapies have been tested in people so Shirley Johnson, RN, the Chief Nursing Officer overseeing the City of Hope program, says you need to have specially trained staff involved.

“We really look to our research patients as being our heroes and particularly our patients that are participating in those first-in-human studies. So having nurses who understand the study protocols, who understand the potential side effects that might be occurring, the symptoms that might be manifested are critical points as we think about first-in-human studies and those things that might occur, and then how best to respond to them.”

One of the reasons we are creating the Alpha Stem Cell Clinic network is because it fits in perfectly with our mission of accelerating the development of stem cell therapies to help patients with unmet medical needs. The network will not just focus on planning and carrying out clinical trials, but will also focus on how those treatments will be paid for, so that life-changing therapies won’t cost patients an arm and a leg.

Dr. John Adams, who heads the UCLA-UCI program, says there will be many obstacles to overcome, but that this is an exciting time:

“The idea behind the Alpha Clinics is to provide an infrastructure to accelerate and make it dead easy for the researchers doing this work to get their work done efficiently, effectively and faster, so that it’s more beneficial for the patients who are undergoing the treatment. And certainly it will allow us to collect more data, and better data, during the course of these clinical trials.”

The data gathered in these trials, and the lessons learned in doing them, will then be shared with others in the network to help create a system of best practices, to make it easier to carry out future clinical trials.

As Dr. John Zaia, who heads the program at City of Hope says: “This is really the beginning of a new era, the era of regenerative medicine.”

You can read more about our Alpha Stem Cell Clinic network, and find links to the individual programs here.

Scientists Sink their Teeth into Stem Cell Evolution

Sometimes, answers to biology’s most important questions can be found in the most unexpected of places.

As reported in the most recent issue of the journal Cell Reports, researchers at the University of California, San Francisco (UCSF) and the University of Helsinki describe how studying fossilized rodent teeth has helped them inch closer to grasping the origins of a particular type of stem cell.

Rodents' ever-growing teeth hold clues to the evolution of stem cells, according to a new study.

Rodents’ ever-growing teeth hold clues to the evolution of stem cells, according to a new study.

Understanding the microenvironment that surrounds each stem cell, known as a stem cell niche, is key to grasping the key mechanisms that drive stem cell growth. But as UCSF scientist Ophir Klein explained, many aspects remain a mystery.

“Despite significant recent strides in the field of stem cell biology, the evolutionary mechanisms that give rise to novel stem cell niches remain essentially unexplored,” said Klein, who served as the study’s senior author. “In this study, we have addressed this central question in the fields of evolutionary and developmental biology.”

In this study, Klein and his team focused on the teeth of extinct rodent species. Why? Because many species of rodent—both extinct species and those alive today—have what’s called ‘ever-growing teeth.’

Unlike most mammals, including we humans, the teeth of some rodent species continue to grow as adults—with the help of stem cell ‘reservoir’ hidden inside the root.

And by analyzing the fossilized teeth of extinct rodent species, the researchers could gain some initial insight into how these reservoirs—which were essentially a type of stem cell niche—evolved.

Most stem cell niche studies take cell samples from hair, blood or other live tissue. Teeth, as it turns out, are the only stem cell niches that can be found in fossil form.

In fact, teeth are “the only proxy…for stem cell behavior in the fossil record,” says Klein.

After analyzing more than 3,000 North American rodent fossils that varied in age between 2 and 50 million years ago, the researchers began to notice a trend. The earlier fossils showed short molar teeth. But over the next few million years, the molars began to increase in length. Interestingly, this coincided with the cooling of the climate during the Cenozoic Period. The types of food available in this cooler, drier climate likely became tougher and more abrasive—leading to evolutionary pressures that selected for longer teeth. By 5 million years ago, three-quarters of all species studied had developed the capability for ever-growing teeth.

The team’s models suggest that this trend has little chance of slowing down, and predicts that more than 80% of rodents will adopt the trait of ever-growing teeth.

The next step, says Klein, is to understand the genetic mechanism that is behind the evolutionary change. He and his team, including the study’s first author Vagan Tapaltsyan, will study mice to test the link between the genetics of tooth height and the appearance of stem cell reservoirs.