Pushing, pulling and dragging stem cell research forward

Government agencies are known for many things, but generally speaking a willingness to do some voluntary, deep self-examination is not one of them. However, for the last few weeks CIRM has been doing a lot of introspection as we develop a new Strategic Plan, a kind of road map for where we are heading.

Patient Advocate meeting in Los Angeles: Photo courtesy Cristy Lytal USC

Patient Advocate meeting in Los Angeles:
Photo courtesy Cristy Lytal USC

But we haven’t been alone. We’ve gone to San Diego, Los Angeles and San Francisco to talk to Patient Advocates in each city, to get their thoughts on what we need to focus on for the future. Why Patient Advocates? Because they are the ones with most skin in the game. They are why we do this work so it’s important they have a say in how we do it.

As Chris Stiehl, a Patient Advocate for type 1 diabetes, said in San Diego: “Let the patient be in the room, let them be part of the conversation about these therapies. They are the ones in need, so let them help make decisions about them right from the start, not at the end.”

A Strategic Plan is, on the surface, a pretty straightforward thing to put together. You look at where you are, identify where you want to go, and figure out the best way to get from here to there. But as with many things, what seems simple on the surface often turns out to be a lot more complicated when looked at in more depth.

The second bit, figuring out where you want to go, is easy. We want to live up to our mission of accelerating the development of stem cells therapies to patients with unmet medical needs. We don’t want to be good at this. We want to be great at this.

Dr. C. Randal Mills talking to Patient Advocates in LA: Photo courtesy Cristy Lytal, USC

Dr. C. Randal Mills talking to Patient Advocates in LA: Photo courtesy Cristy Lytal, USC

The first part, seeing where you are, is a little tougher: it involves what our President and CEO, Dr. Randy Mills, “confronting some brutal facts”, being really honest in assessing where you are because without that honesty you can’t achieve anything.

So where are we as an agency? Well, we have close to one billion dollars left in the bank, we have 12 projects in clinical trials and more on the way, we have helped advance stem cells from a fledgling field to a science on the brink of what we hope will be some remarkable treatments, and we have a remarkable team ready to help drive the field still further.

But how do we do that, how do we identify the third part of the puzzle, getting from where we are to where we want to be? CIRM 2.0 is part of the answer – developing a process to fund research that is easier, faster and more responsive to the needs of the scientists and companies developing new therapies. But that’s just part of the answer.

Some of the Patient Advocates asked if we considered focusing on just a few diseases, such as the ten largest killers of Americans, and devoting our remaining resources to fixing them. And the answer is yes, we looked at every single option. But we quickly decided against that because, as Randy Mills said:

“This is not a popularity contest, you can’t judge need by numbers, deciding the worth of something by how many people have it. We are disease agnostic. What we do is find the best science, and fund it.”

Another necessary element is developing better ways to attract greater investment from big pharmaceutical companies and venture capital to really help move the most promising projects through clinical trials and into patients. That is starting to happen, not as fast as we would like, but as our blog yesterday shows things are moving in this direction.

And the third piece of the pie is getting these treatments through the regulatory process, getting the Food and Drug Administration (FDA) to approve therapies for clinical trials. And this last piece clearly hit a nerve.

Many Patient Advocates expressed frustration at the slow pace of approval for any therapy by the FDA, some saying it felt like they just kept piling up obstacles in the way.

Dr. Mills said the FDA is caught between a rock and a hard place; criticized if it approves too slowly and chastised if it approves too fast, green lighting a therapy that later proves to have problems. But he agreed that changes are needed:

“The regulatory framework works well for things like drugs and small molecules that can be taken in pills but it doesn’t work well for cellular therapies like stem cells. It needs to do better at that.”

One Advocate suggested a Boot Camp for researchers, drilling them in the skills they’ll need to get FDA approval. Others suggested applying political pressure from Patient Advocacy groups to push for change.

As always there are no easy answers, but the meeting certainly raised many great questions. Those are all helping us focus our thinking on what needs to be in the Strategic Plan.

Randy ended the Patient Advocate events by saying the stem cell agency “is in the time business. What we do is time sensitive.” For too many people that time is already running out. We have to do everything we can to change that.

Partnering with Big Pharma to benefit patients

Our mission at CIRM is to accelerate the development of stem cell therapies for patients with unmet medical needs. One way we have been doing that is funding promising research to help it get through what’s called the “Valley of Death.” This is the time between a product or project showing promise and the time it shows that it actually works.

Many times the big pharmaceutical companies or deep pocketed investors, whose support is needed to cover the cost of clinical trials, don’t want to get involved until they see solid proof that this approach works. However, without that support the researchers can’t do the early stage clinical trials to get that proof.

The stem cell agency has been helping get these projects through this Catch 22 of medical research, giving them the support they need to get through the Valley of Death and emerge on the other side where Big Pharma is waiting, ready to take them from there.

We saw more evidence that Big Pharma is increasingly happy doing that this week with the news that the University of California, San Diego, is teaming up with GSK to develop a new approach to treating blood cancers.

Dr. Catriona Jamieson: Photo courtesy Moores Cancer Center, UCSD

Dr. Catriona Jamieson:
Photo courtesy Moores Cancer Center, UCSD

Dr. Catriona Jamieson is leading the UCSD team through her research that aims at killing the cancer stem cells that help tumors survive chemotherapy and other therapies, and then spread throughout the body again. This is work that we have helped fund.

In a story in The San Diego Union Tribune, reporter Brad Fikes says this is a big step forward:

“London-based GSK’s involvement marks a maturation of this aspect of Jamieson’s research from basic science to the early stages of discovering a drug candidate. Accelerating such research is a core purpose of CIRM, founded in 2004 to advance stem cell technology into disease therapies and diagnostics.”

The stem cell agency’s President and CEO, Dr. C. Randal Mills, is also quoted in the piece saying:

“This is great news for Dr. Jamieson and UCSD, but most importantly it is great news for patients. Academic-industry partnerships such as this bring to bear the considerable resources necessary to meaningfully confront healthcare’s biggest challenges. We have been strong supporters of Dr. Jamieson’s work for many years and I think this partnership not only reflects the progress that she has made, but just as importantly it reflects how the field as a whole has progressed.”

As the piece points out, academic researchers are very good at the science but are not always as good at turning the results of the research into a marketable product. That’s where having an industry partner helps. The companies have the experience turning promising therapies into approved treatments.

As Scott Lippman, director of the Moores Cancer Center at UCSD, said of the partnership:

“This is a wonderful example of academia-industry collaboration to accelerate drug development and clinical impact… and opens the door for cancer stem cell targeting from a completely new angle.”

With the cost of carrying out medical research and clinical trials rising it’s hard for scientists with limited funding to go it alone. That’s why these partnerships, with CIRM and industry, are so important. Working together we make it possible to speed up the development and testing of therapies, and get them to patients as quickly as possible.

Share your voice, shape our future

shutterstock_201440705There is power in a single voice. I am always reminded of that whenever I meet a patient advocate and hear them talk about the need for treatments and cures – and not just for their particular disease but for everyone.

The passion and commitment they display in advocating for more research funding reflects the fact that everyday, they live with the consequences of the lack of effective therapies. So as we at CIRM, think about the stem cell agency’s future and are putting together a new Strategic Plan to help shape the direction we take, it only makes sense for us to turn to the patient advocate community for their thoughts and ideas on what that future should look like.

That’s why we are setting up three meetings in the next ten days in San Diego, Los Angeles and San Francisco to give our patient advocates a chance to let us know what they think, in person.

We have already sent our key stakeholders a survey to get their thoughts on the general direction for the Strategic Plan, but there is a big difference between ticking a box and having a conversation. These upcoming meetings are a chance to talk together, to explore ideas and really flesh out the details of what this Strategic Plan could be and should be.

Our President and CEO, Dr. C. Randal Mills wants each of those meetings to be an opportunity to hear, first hand, what people would like to see as we enter our second decade. We have close to one billion dollars left to invest in research so there’s a lot at stake and this is a great chance for patient advocates to help shape our next five years.

Every voice counts, so join us and make sure that yours is heard.

The events are:

San Diego, Monday, July 13th at noon at Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037

Los Angeles: Tuesday, July 14th at noon at Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at USC, 1425 San Pablo Street, 1st floor conf. room Los Angeles, CA 90033

San Francisco: Wednesday, July 15th at noon at CIRM, 210 King Street (3rd floor), San Francisco, CA 94107

There will be parking at each event and a light lunch will be served.

We hope to see you at one of them and if you do plan on coming please RSVP to info@cirm.ca.gov

And of course please feel free to share this invitation to anyone you think might be interested in having their voice heard. We all have a stake in this.

Creative partnerships that promote progress

Lewis and Clark: great partnerships can change the world

Lewis and Clark: great partnerships can change the world

Having a good partner can turn something good into something truly memorable. Where would Laurel be without Hardy, Lewis without Clark, Butch Cassidy without the Sundance Kid. That’s why the stem cell agency has partnerships on a number of different levels as part of our mission of accelerating the development of stem cell cures to patients with unmet medical needs.

Our latest partnership is with RegMedNet which, in its own words, “provides a unique and unparalleled platform for the regenerative medicine community to share insights, discuss the latest research, and help move the field forward.” With a goal like that why would we not want to support them?

Like us RegMedNet believes that regenerative medicine is going to completely change the way we treat disease, even the way we think about disease. They also believe that progress of the kind we all want is only going to come by bringing together all the key players from the researchers and manufacturers, to the government regulators and, of course, the patient advocates. Each has a vital role to play in moving the field forward and RegMedNet reflects that in both the content it posts online and in the contributors, who represent institutions and companies worldwide.

One of the most important elements in any partnership is understanding, and RegMedNet does a great job of trying to raise awareness about the field, the challenges we all face, and the progress being made. Bringing together so many different perspectives in one spot really helps create a much deeper understanding of regenerative medicine as a whole.

In a few short years regenerative medicine has gone from a relatively small field to a global industry. Our hope is that creating partnerships with like-minded groups around the world, is going to help it get even bigger and, even better.

New tech tool speeds up stem cell research

It’s hard to do a good job if you don’t have the right tools. Now researchers have access to a great new tool that could really help them accelerate their work, a tool its developers say “will revolutionize the way cell biologists develop” stem cell models to test in the lab.

Fluidigm's Castillo system

Fluidigm’s Callisto system

The device is called Callisto™. It was created by Fluidigm thanks to two grants from CIRM. The goal was to develop a device that would allow researchers more control and precision in the ways that they could turn stem cells into different kinds of cell. This is often a long, labor-intensive process requiring round-the-clock maintenance of the cells to get them to make the desired transformation.

Callisto changes that. The device has 32 chambers, giving researchers more control over the conditions that cells are stored in, even allowing them to create different environmental conditions for different groups of cells. All with much less human intervention.

Lila Collins, Ph.D., the CIRM Science Officer who has worked closely with Fluidigm on this project over the years, says this system has some big advantages over the past:

“Creating the optimal conditions for reprogramming, stem cell culture and stem cells has historically been a tedious and manually laborious task. This system allows a user to more efficiently test a variety of cellular stimuli at various times without having to stay tied to the bench. Once the chip is set up in the instrument, the user can go off and do other things.”

Having a machine that is faster and easier to use is not the only advantage Callisto offers, it also gives researchers the ability to systematically and simultaneously test different combinations of factors, to see which ones are most effective at changing stem cells into different kinds of cell. And once they know which combinations work best they can use Callisto to reproduce them time after time. That consistency means researchers in different parts of the world can create cells under exactly the same conditions, so that results from one study will more readily support and reflect results from another.

In a news release about Callisto,  Fluidigm’s President and CEO Gajus Worthington, says this could be tremendously useful in developing new therapies:

“Fluidigm aims to enable important research that would otherwise be impractical. The Callisto system incorporates some of our finest microfluidic technology to date, and will allow researchers to quickly and easily create complex cell culture environments. This in turn can help reveal how stems cells make fate decisions. Callisto makes challenging applications, such as cellular reprogramming and analysis, more accessible to a wide range of scientists. We believe this will move biological discovery forward significantly.”

And as Collins points out, Callisto doesn’t just do this on a bulk level, working with millions of cells at a time, the way the current methods do:

“Using a bulk method it’s possible that one might miss an important event in the mixture. The technology in this system allows the user to stimulate and study individual cells. In this way, one could measure changes in small sub-populations and find ways to increase or decrease them.”

Having the right tools doesn’t always mean you are going to succeed, but it certainly makes it a lot easier.

Stem cell stories that caught our eye: regenerating limbs on scaffolds, self regeneration via a drug, mood stem cells, CRISPR

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.

Regenerating a limb, or at least part of it. Many teams have generated organs or parts of organs in animals by starting with a dead one. They literally wash away all the cells from the donor organ using a detergent so that they are left with a framework of the cells’ connective tissue. Then they seed that scaffold with stem cells or other cells to grow a new organ. A team at Massachusetts General Hospital has now used the same process to generate at least part of a rat limb.

The news cells growing on the donor limb scaffold in a bioreactor

The news cells growing on the donor limb scaffold in a bioreactor

It took a week to get the tiny little leg fully cleaned up and then another two weeks for the seeded cells to repopulate the scaffold left behind. That cellular matrix seems to send signals to the seeded cells on what type of tissue to become and how to arrange themselves. The team succeeded in creating an artificial limb with muscle cells aligned into appropriate fibers and blood vessels in the right places to keep them nourished. The researchers published their work in the journal Biomaterials and the website Next Big Future wrote up the procedure and provided some context on the limitations of current prosthetic limbs. The author also notes that the researchers have a lot more work to do, notably to prove they can get nerves to grow and connect at the point of transplantation to the “patient” animal. Discover also wrote a version of the story.

Getting the body to regenerate itself. A strain of mice discovered 20 years ago has led a multi-institution team to a possible way to get the body to regenerate damaged tissue, something the mouse discovered two decades ago can do and other mammals cannot. The researchers found that those mice have one chemical pathway, HIF-1a, that is active in the adult mice but is normally only active in the developing embryo. When they pushed that chemical path to work in normal mice those mice, too, gained the power to regenerate tissue. Ellen Heber-Katz from the Lankenau Institute for Medical Research outside of Philadelphia was quoted in the institute’s press release on Health Medicine Network.

“We discovered that the HIF-1a pathway–an oxygen regulatory pathway predominantly used early in evolution but still used during embryonic development–can act to trigger healthy regrowth of lost or damaged tissue in mice, opening up new possibilities for mammalian tissue regeneration.”

Heber-Katz led the team that included researchers from the company Allergan and the University of California, Berkeley. In order to activate the HIF-1a pathway they basically took the natural brakes off it. Another cellular chemical, PHD normally inhibits the action of HIF-1a in adults. The researcher turned the table on PHD and inhibited it instead. The result, after three injections of the PHD inhibitor over five days the mice who had a hole punched in their ear healed over the hole complete with cartilage and new hair.

Regulating memory and mood. It turns out your brain’s hippocampus, the section responsible for both memory and mood, has not one type of stem cell replenishing nerves, but two. And those two types of stem cells give rise to different types of nerves, which may account for the highly varied function of this part of the brain. Researchers at the University of Queensland in Australia isolated the two types of stem cells and then let them grow into nerves but the nerves from each expressed different genes, which means they have different functions. The lead researcher on the study, Dhanisha Jhaveri, discussed the findings in a press release picked up by Science Daily:

“The two cell groups are located in different regions of the hippocampus, which suggests that distinct areas within the hippocampus control spatial learning versus mood.”

The research provides fodder for future work looking into the treatment of learning and mood disorders. Review of the now celebrity tool, CRISPR. I don’t think I have ever seen so much ink and so many electrons spilled over a science tool as I have seen for CRISPR, particularly for one few scientists can tell you what the acronym stands for: Clustered Regularly Interspaced Short Palindromic Repeats. It is basically a fluke in the genes of several bacteria in which some of the base pairs that make up their DNA get repeated at regular intervals. Their configuration confers the ability for CRISPR segments to be used to disrupt or change specific genes in other organisms. Heidi Ledford writing for Nature in the journal’s news section provides a great wrap-up of what the technology is and what it can do, but also provides some caveats about its efficiency, accuracy, ethical concerns, and occasionally just not understanding how it works. The Nature team provides some valuable infographics showing the history of the science and on the rapid adoption of the technology as shown in publications, patents and funding. They also published an infographic on using CRISPR for “gene drive,” a way to push a modified trait through a population quickly, such as a mutation that could stop mosquitos from transmitting malaria. This potential drives much of the concern about misuse of the tool. But scientists quoted in the piece also provide more mundane reasons for moving slowly in thinking about using the therapy for patients. One of those is that it can sometime cause a high rate of “off-target” gene edits; simply put, cutting DNA in the wrong place. But as a research tool, there is no doubt it has revolutionized the field of gene modification. It is so much faster and so much cheaper than earlier gene editing tools; it is now possible for almost any lab to do this work. The piece starts out with an anecdote from CIRM-grantee Bruce Conklin of the Gladstone Institutes, talking about how it completely changed the way his lab works.

“It was a student’s entire thesis to change one gene,” Conklin said, adding “CRISPR is turning everything on its head.”

Two for 2.0 and Two for us

It began as an ambitious idea; yesterday it became a reality when the CIRM Board approved two projects under CIRM 2.0, one of them a Phase 3 clinical trial for a deadly form of skin cancer.

Just to recap, CIRM 2.0 was introduced by Dr. C. Randal Mills when he took over as President and CEO of the stem cell agency last year. The idea is to speed up the way we work, to get money to the most promising therapies and the best science as quickly as possible. It puts added emphasis on speed, patients and partnerships.

Yesterday our Board approved the first two projects to come before them under this new way of working. One was for almost $18 million for NeoStem, which is planning a Phase 3 clinical trial for metastatic melanoma, a disease that last year alone claimed more than 10,000 lives in the U.S.

This will be the first Phase 3 trial we have funded so clearly it’s quite a milestone for us and for NeoStem. If it proves effective in this trial it could well be approved by the Food and Drug Administration (FDA) for use in melanoma patients. The therapy itself is unique in that it uses the patient’s own tumor cells to create a personalized therapy, one that is designed to engage the patient’s immune system and destroy the cancer.

The Board also approved almost $5 million for Cedars-Sinai in Los Angeles to do the late-stage research needed to apply to the FDA for approval for a clinical trial to treat retinitis pigmentosa (RP). RP is a nasty, degenerative condition that slowly destroys a patient’s vision. There is no cure and no effective therapy.

We are currently funding another clinical trial in this area. The two projects use different types of cells and propose different methods of reducing RP’s devastation. CIRM has a record of trying multiple routes to achieve success when dealing with unmet medical needs.

As Dr. Mills said in a news release, both the therapies approved for funding yesterday support our mission:

“CIRM 2.0 is designed to accelerate the development of treatments for people with unmet medical needs, and these two projects clearly fit that description. With the Board’s approval today we will now get this work up and running within the next 45 days. But that’s just the start. We are not just providing financial support, we are also partnering with these groups to provide expertise, guidance and other kinds of support that these teams need to help them be successful. That’s the promise of CIRM 2.0. Faster funding, better programs and a more comprehensive approach to supporting their progress.”

CIRM Chair Jonathan Thomas swearing in new Board members Adriana Padilla and Bob Price

CIRM Chair Jonathan Thomas swearing in new Board members Adriana Padilla and Bob Price

Two seemed to be the number of the day yesterday with the Board welcoming two new members.

Dr. Adriana Padilla is the new Patient Advocate Board member for type 2 Diabetes. She’s a family physician, a member of the University of California, San Francisco-Fresno medical faculty, and an award-winning researcher with expertise in diabetes and its impact on Latino families and the health system in California’s Central Valley. She is also active in the National Hispanic Medical Association (NHMA) and is also a member of the American Diabetes Association.

Dr. Padilla said she hopes her presence will help increase awareness among Latinos of the importance of the work the agency is doing:

“When I was asked about being on the Board I did some research to find out more and it was really touching to learn about some of the exciting work that has been done by the agency and the possibilities that can be done for patients, including those I serve, members of the Latino community.”

Dr. Bob Price is the Associate Vice Chancellor for Research and a Professor of Political Science at U.C. Berkeley. His academic and teaching interests include comparative politics, with a particular interest in the politics of South Africa. This is Dr. Price’s second time on the Board.  He previously served as the alternate to UC Berkeley Chancellor Robert Birgeneau.

Although he has only been off the Board for a little more than a year Dr. Price said he is aware of the big changes that have taken place in that time and is looking forward to being a part of the new CIRM 2.0.

How stimulating! A new way to repair broken bones

For those of us who live in earthquake country the recent devastating quakes in Nepal are a reminder, as if we needed one, of the danger and damage these temblors can cause. Many of those injured in the quake suffered severe bone injuries – broken legs, crushed limbs etc. Repairing those injuries is going to take time and expert medical care. But now a new discovery is opening up the possibility of repairing injuries like this, even regenerating the broken bones, in a more efficient and effective way.

shutterstock_18578173A study published in Scientific Reports  shows that it is possible to regrow bone tissue using protein signals from stem cells. Even more importantly is that this new bone tissue seems to be just as effective, in terms of the quantity and quality of the bone created, as the current methods.

In a news release senior author Todd McDevitt, Ph.D., said this shows we might not even need whole stem cells to regenerate damaged tissue:

“This proof-of-principle work establishes a novel bone formation therapy that exploits the regenerative potential of stem cells. With this technique we can produce new tissue that is completely stem cell-derived and that performs similarly with the gold standard in the field.”

McDevitt – who is now at the Gladstone Institutes thanks to a research leadership award from CIRM  – extracted the proteins that stem cells produce to help regenerate damaged tissues. They then isolated the particular factors they needed to help regenerate bones, in this case bone morphogenetic protein or BMP. That BMP was then transplanted into mice to stimulate bone growth. And it worked.

While this compares favorably to current methods of regenerating or repairing damaged bones it has a few advantages. Current methods rely on getting bones from cadavers and grinding them up to get the growth factors needed to stimulate bone growth. But bones from cadavers can often be in short supply and the quality is highly variable.

As McDevitt says:

“These limitations motivate the need for more consistent and reproducible source material for tissue regeneration. As a renewable resource that is both scalable and consistent in manufacturing, pluripotent stem cells are an ideal solution.”

He says the next step is to build on this research, and try to find ways to make this method even more efficient. If he succeeds he says it could open up new ways of treating devastating injuries such as those sustained by soldiers in battle, or by earthquake victims.

A hopeful sight: therapy for vision loss cleared for clinical trial

Rosalinda Barrero

Rosalinda Barrero, has retinitis pigmentosa

Rosalinda Barrero says people often thought she was rude, or a snob, because of the way she behaved, pretending not to see them or ignoring them on the street. The truth is Rosalinda has retinitis pigmentosa (RP), a nasty disease, one that often attacks early in life and slowly destroys a person’s vision. Rosalinda’s eyes look normal but she can see almost nothing.

“I’ve lived my whole life with this. I told my daughters [as a child] I didn’t like to go Trick or Treating at Halloween because I couldn’t see. I’d trip; I’d loose my candy. I just wanted to stay home.”

Rosalinda says she desperately wants a treatment:

“Because I’m a mom and I would be so much a better mom if I could see. I could drive my daughters around. I want to do my part as a mom.”

Now a promising therapy for RP, funded by the stem cell agency, has been cleared by the Food and Drug Administration (FDA) to start a clinical trial in people.

The therapy was developed by Dr. Henry Klassen at the University of California, Irvine (UCI). RP is a relatively rare, inherited condition in which the light-sensitive cells at the back of the retina, cells that are essential for vision, slowly and progressively degenerate. Eventually it can result in blindness. There is no cure and no effective long-term treatment.

Dr. Klassen’s team will inject patients with stem cells, known as retinal progenitors, to help replace those cells destroyed by the disease and hopefully to save those not yet damaged.

In a news release about the therapy Dr. Klassen said the main goal of this small Phase I trial will be to make sure this approach is safe:

“This milestone is a very important one for our project. It signals a turning point, marking the beginning of the clinical phase of development, and we are all very excited about this project.”

Jonathan Thomas, the Chair of our Board, says that CIRM has invested almost $20 million to help support this work through early stage research and now, into the clinic.

“One of the goals of the agency is to provide the support that promising therapies need to progress and ultimately to get into clinical trials in patients. RP affects about 1.5 million people worldwide and is the leading cause of inherited blindness in the developed world. Having an effective treatment for it would transform people’s lives in extraordinary ways.”

Dr. Klassen says without that support it is doubtful that this work would have progressed as quickly as it has. And the support doesn’t just involve money:

“CIRM has played a critical and essential role in this project. While the funding is extremely important, CIRM also tutors and guides its grantees in the many aspects of translational development at every step of the way, and this accelerates during the later pre-clinical phase where much is at stake.”

This is now the 12th project that we are funding that has been approved by the FDA for clinical trials. It’s cause for optimism, but cautious optimism. These are small scale, early phase trials that in many cases are the first time these therapies have been tested in people. They look promising in the lab. Now it’s time to see if they are equally promising in people.

Considering we didn’t really start funding research until 2007 we have come a long way in a short time. Clearly we still have a long way to go. But the news that Dr. Klassen’s work has been given the go-ahead to take the next, big step, is a hopeful sign for Rosalinda and others with RP that we are at least heading in the right direction.

One of our recent Spotlight on Disease videos features Dr. Klassen and Rosalinda Barrero talking about RP.

This work will be one of the clinical trials being tested in our new Alpha Stem Cell Clinic Network. You can read more about that network 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.