Stem cell stories that caught our eye: two new approaches to treating diabetes and a video on why this work excites

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.

Insulin producing cells avoid immune rejection. The phrase, there is more than one way to skin a cat often applies to the science of trying to develop therapies. A CIRM-funded team at the company Viacyte is working to cure diabetes and has developed a cell line that is a middleman, or precursor cell, part way between a stem cell and a fully mature insulin-producing cell. When transplanted into animal patients it has been shown to mature into the needed cells and correct the faulty sugar levels caused by the disease.

But, the company could not just transplant those cells into patients whose own insulin-producing cells had been destroyed by their immune system without protecting them from that immune attack. In a human trial we are funding that began in September the Viacyte team protects the cells inside a small porous pouch placed under the skin.

Insulin-producing cells shown in green surviving after transplant because of the new procedure.

Insulin-producing cells shown in green surviving after transplant because of the new procedure.

Now they have reported in Cell Stem Cell work done with researchers at the University of California, San Francisco that shows that a drug-like pretreatment can alter the animal’s immune response and let the new cells survive without the protective pouch. Those cells, called PEC-01, were protected by agents that blocked a very specific part of the immune system that causes immune rejection—a much gentler treatment than the immune suppression used for organ transplants.

The San Diego Union Tribune did a nice job of putting the two approaches into perspective, and Reuters picked up the company’s press release that quotes the senior UCSF researcher Jeffrey Bluestone:

“The demonstration that these new immunotherapies block specific pathways and immune cells that are responsible for attacking pancreatic islet cells and prevent the rejection of implanted PEC-01 cells is an exciting finding that could lead to advances in the way we treat diabetes and other diseases.”

Stem cell work a runner up for discovery of the year. Each year the journal Science names a discovery of the year and nine runners up. This year the Mars rover took top honors but a Harvard team scored a runner up slot for its work creating mature insulin producing cells from stem cells in the lab. Many labs had failed to accomplish this feat over the past several years.

I agree this is a big deal, but many researchers in the field believe that the best place to mature stem cells into the desired tissue is in the patient where they can take cues from the body that are much more complex than what we can recreate in the lab. The Viacyte team cited above uses the in-the-body approach and is already testing the therapy in patients.

Toward the end of the original Harvard press release and at the end of the notice in Science, the authors note that before the work can be used in patients they need to overcome the patient’s immune reaction—something the most recent Viacyte discovery might be able to help achieve.

Clue found for how stem cells make decisions.
Many a researcher has used the Bizarro cartoon labeled “Stem Cell Parental Advice” with the thought balloon “You are a stem cell you can become anything you want when you grow up.” Researchers have found that ability to be a double-edged sword. Since stem cells can become anything it is often hard to direct them efficiently down a particular desired path.

Now a Danish team from the University of Copenhagen has documented in Cell Reports a way to block all the various maturation paths and keep the stem cells in a stem cell state. This could be a first step to being able to consistently direct them down one preferred path. Science Codex picked up the university’s press release, which quoted a member of the research team, Joshua Brickman on why this could be valuable:

“If you block all the choices they can make, they stay in the stem cell state. If you only allow them one door to exit from the stem cell state, you should be able to make particular cell types more efficiently. So if you only leave one door open then it’s the path of least resistance and when you give them a push they really go.”

Video captures the excitement of stem cell researchers. Stanford’s research blog Scope produced a fun end-of-the-year piece that includes a video of researcher Margaret Fuller describing why she is so excited to work in this field. One example she cites came from a recent report about using stem cells to help repair lost muscle in wounded soldiers returning from Afghanistan. I’ll let you watch the video to see why she said “It gives me chills just thinking about it.”

CIRM-Funded UC-Irvine Team Set to Launch Stem Cell Trial for Retinitis Pigmentosa in 2015

Rosalinda Barrero has often been mistaken for a rude snob. She has the habit of not saying hello or even acknowledging the presence of acquaintances that she passes around town. But in fact this kind, loving mom of three has been steadily losing her vision over a lifetime. And she doesn’t seem blind because people are still vaguely visible as shadowy ghosts but their faces are unrecognizable.

RosalindaBarrero_blog

Rosalinda Barrero is legally blind due to retinitis pigmentosa. She eagerly awaits the launch of a CIRM-funded trial that will test a candidate stem cell-based treatment.

Barrero is stricken with retinitis pigmentosa (RP) an incurable genetic disease that gradually destroys the light sensing nerve cells, called photoreceptors, located in the retina at the back of the eye. In October, Rosalinda and her husband German spoke to the CIRM governing Board about the devastating impact of RP on their lives and their excitement about a soon to begin CIRM-funded stem cell-based clinical trial for the treatment of RP. The project is headed by UC-Irvine associate professor Henry Klassen, MD, PhD, who also spoke to the Board. Videos of their presentations are now available on our website and below:

Over 3000 known genetic mutations can give rise to RP. These mutations lead to the gradual deterioration of the so-called rod photoreceptors. These rod cells specifically provide our night vision — like on a moonless night. Rosalinda clearly remembers her childhood struggles with night blindness on Halloween:

“I didn’t like trick-or-treating because I couldn’t see in the dark. I ‘d say ‘this is not fun! I’m tripping! I’m losing all my candy!’ I wanted to stay home and hand out candy”

Unfortunately the disease doesn’t stop there. As the rods continue to die off another type of photoreceptor, the cone cells, become innocent bystanders and also gradually deteriorate later in life. As Dr. Klassen explained, it’s the cone cells that are critical for our sight:

“The cones are what humans use for almost all of their vision. Even at night when you’re driving a car with headlights you’re using mainly your cones. So if we could preserve the cones we can really help the patient.”

With the support of a $17 million CIRM Disease Team grant, Klassen and his team anticipates starting a stem-call based clinical trial in early 2015 with the ultimate aim of healing those cone cells in RP patients. The therapy uses a type of immature stem cell of the retina called retinal progenitor cells. The proposed approach relies on the injection of the cells into the jelly of the eye near the retina to promote indirect healing. Klassen explained the project rationale to the Board:

“So we’re talking about little clusters of cells that could fit on the head of a pin in the jelly of the eye and they’re just floating there. And what are they going to do? Well they just sit there and secrete all the factors they normally secrete during retinal development and diffuse into the retina. Once in the retina we believe [based on animal studies] those factors are going to reprogram the photoreceptors into becoming functional again instead of going down that road where they’re going to commit suicide.”

Rosalinda is beyond thrilled with the prospect of being a recipient of this candidate therapy. Her husband German echoed her hopefulness to the Board:

“Even though it’s not a deadly disease, [the therapy] would be life-changing not only for Rosie it would be for everyone around her. “

To learn more about CIRM-funded research related to blindness, visit our fact sheet.

‘Tis the Season to Talk Science

And just like that another holiday season is upon us. It’s that time of year when scientists across the nation sit down for their family holiday dinner and attempt to answer the following question without triggering blank stares around the dining room table: “So dear, tell me again, what is it that you do in your laboratory?”

KDubbin bench800x800

Karen Dubbin, a Stanford PhD candidate in the CIRM-funded lab of Sarah Heilshorn, is happy about the valuable new skills she gained in a recent Public Communications of Research course

For some researchers, like those launching clinical trials for incurable diseases, their answers are as easy to digest as grandma’s mashed potatoes. But for others who work on less tangible but equally important areas of science, like chemistry, getting through to the family can be challenging—not just family but the public in general. And that’s a problem. Karen Dubbin, a Stanford University Ph.D. candidate studying materials science and engineering (fields that utilize chemistry) recognizes the importance of communicating her work to the public:

“I think that it is important to communicate research in a way the public can understand primarily because the public funds most of the research I participate in, and in order to spread the awareness of need for scientific funding (and hopefully increase said funding in the future) one has to be able to explain it in a way that excites the average person. “

Dubbin just completed a new, mini-course offered to Stanford graduate students in the departments of chemistry, chemical engineering, and chemical biology to help them work on communicating their research with the public. The class came about through a conversation between chemistry professor Chaitan Khosla and my former CIRM colleague Amy Adams who is now director of Interdisciplinary Life Sciences Communications at Stanford. During their conversation, they mulled over why chemists have a steeper hill to climb when communicating their work. Adams said they reached this conclusion:

“Biology always has the hook of being about you, and physics has an “oh wow” factor. Chemistry is somehow always a bit more removed from human problems and also less wow-ish. That said, it’s important to just about everything we do – the keyboard I’m typing on, parts of my clothes, my health.”

And so the Public Communications of Research course was born. Adams brought in science communicators from across the Stanford campus to talk about writing, video and social media, and to help the students think through how they would communicate their own science. As part of a final assignment, Dubbin produced the video below, which summarizes her work in the CIRM-funded lab of Sarah Heilshorn. Her video uses fun graphics and succinct text to explain how the design of new biomaterials is critical for the efficient delivery of future stem cell-based treatments to patients.

Dubbin thought the course was “super helpful” and she gained an important insight about science communication:

“I think when I used to try to explain my research to non-scientists, being totally accurate was the most important thing to me. Now I think it’s more important to make sure the main ideas are extra clear, as you can always go back and answer questions on the more intricate details if the listener is interested.”

Now that her parents and extended family all have copies of the video, Dubbin can look forward to bright eyes instead of blank stares as she touches upon those more intricate details at this year’s holiday dinner.

Key stem cell gene controlled from afar, Canadian scientists discover

Embryonic stem cells can, by definition, mature into any cell type in the body. They are able to maintain this state of so-called pluripotency with the help of a gene called Sox2. And now, researchers at the University of Toronto (U of T) have discovered the unseen force that controls it. These findings, reported in the latest issue of Genes & Development, offer much-needed understanding of the steps a cell must take as it grows up.

Mouse embryonic stem cells grown in a round colony of cells (A) and express Sox2 (B), shown in red. Sox2 control region (SCR)-deleted cells have lost the typical appearance of embryonic stem cells (C) and do not express Sox2 (D). [Credit: Jennifer Mitchell/University of Toronto]

Mouse embryonic stem cells grown in a round colony of cells (A) and express Sox2 (B), shown in red. Sox2 control region (SCR)-deleted cells have lost the typical appearance of embryonic stem cells (C) and do not express Sox2 (D). [Credit: Jennifer Mitchell/University of Toronto]

Led by U of T Professor Jennifer Mitchell, the research team were, for the first time, able to identify the specific molecular regulator that switched the Sox2 gene on and off at specific times during an embryonic cell’s lifetime. As Mitchell explained:

“We studied how the Sox2 gene is turned on in mice, and found the region of the genome that is needed to turn the gene on in embryonic stem cells. Like the gene itself, this region of the genome enables these stem cells to maintain their ability to become any type of cell.”

The team named this region the Sox2 control region, or SCR.

For the last decade scientists have been using knowledge gleaned from the Human Genome Project to map how and when genes are switched on and off. Interestingly, the regions that control the gene in question aren’t always located close by.

This was the case with Sox2, said Mitchell. Early on, researchers had argued that Sox2 was regulated from nearby. But in this study, the team found the SCR, which controls Sox2, to be located more than 100,000 DNA base pairs away. According to Mitchell, the process by which the SCR activates Sox2 is fascinating:

“To contact the gene, the DNA makes a loop that brings the SCR close to the gene itself only in embryonic stem cells… It is possible that the formation of the loop needed to make contact with the Sox2 gene is an important final step in the process by which researchers practicing regenerative medicine can generate pluripotent cells from adult cells.”

Indeed, despite a flurry of research breakthroughs and a promising number of clinical trials moving forward, there are still some fundamental aspects of stem cell biology that remain unknown. This discovery, argues Mitchell, is an important step towards reaching toward improving the way in which scientists manipulate stem cells to treat disease.

Maintaining the momentum: a good start but CIRM 2.0 is just the first step

Sir Isaac Newton

Sir Isaac Newton

Newton’s First Law of Physics states that an object either remains at rest or continues to move at a constant velocity unless acted upon by an external force. Well, for the stem cell agency the external force was an exercise in thinking differently about how we do business. That resulted in our governing Board approving CIRM 2.0 yesterday. And we intend to keep that momentum going for as long as we can.

CIRM 2.0 is a streamlined process that will make it easier and faster to apply for funding from the stem cell agency, and is designed to attract high quality clinical stage projects that are ready to start within 45 days of being approved for funding.

As our President and CEO Dr. C. Randal Mills said in a news release:

“Our mission is to accelerate the development of stem cell treatments for patients with unmet medical needs. With many of these diseases, time lost waiting for a treatment means lives lost. We must continue to find new and innovative ways to speed up our process and make it easier to get promising therapies into clinical trials, and to give them all the support they need to be successful. That’s why we undertook this radical overhaul of the way we do business.”

In the past it could take up to two years for a researcher or company to move from applying for funding to getting the money as part of an approved contract. CIRM 2.0 simplifies and accelerates the process, cutting that two years down to just four months. And instead of just one single round of funding with an application deadline every 12-to-18 months, CIRM 2.0 will have an open application process for clinical stage programs with deadlines every month. That means companies and researchers can apply when they are ready and won’t have to try and rush an application in prematurely, for fear it could be another year or more before the chance comes around again.

It’s a big change in the way we work and as Dr. Mills told the Board at yesterday’s meeting, there are bound to be problems:

“There will be bumps in the road, you can’t make radical changes of this nature and scope without running into problems. I know that, my team knows that and we are ready to handle whatever unforeseen consequences come up.”

We plan on monitoring 2.0 as we unveil it, constantly checking to see what’s working and to fix what isn’t. In the short term we will use several measures of how well it’s working such as how many high quality applications we get, how quickly we can move these applications through the approvals process and how long it takes to get successful applicants their money. In the long term the best indication of success will be the quality of the programs we fund and how well they do in completing clinical trials.

This first phase of CIRM 2.0 will cover funding for clinical work but it will later be expanded to include discovery (also known as basic research) and translational research (moving promising discovery research to the clinic). But as Dr. Mills says, even while we are implementing CIRM 2.0 we are already thinking about the next step.

“Soon as this is done we have to start working on how we can improve CIRM 2.0 and keep that sense of urgency and innovation in front of us so that we always look to build a better product and fulfill our mission in a better way. Because there are many sick people out there looking to us for help and until that changes we need to be always looking to improve. Which is why as soon as CIRM 2.0 is done, we’re looking to create CIRM 3.0”

Stem cell stories that caught our eye: good fat vs. bad fat, the black box of cell reprogramming and Parkinson’s

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.

One day a pill might turn bad fat into good fat. For a few years now several research teams have linked white fat to the bad health effects of fat and brown fat to more positive metabolism and to being leaner. Now, a team at the Harvard Stem Cell Institute has used stem cells in the laboratory as a screening tool to look for drugs that could cause the bad fat to turn into the good fat.

Brown fat derived from stem cells. Image courtesy of Harvard

Brown fat derived from stem cells. Image courtesy of Harvard

They have found two molecules that can prevent fat stem cells from becoming mature white fat and instead direct them to become brown fat. But those two molecules used as pills would likely have too many unintended side effects to become a treatment that would likely need to be taken long-term. So, despite some overblown headlines about a “pill to replace a treadmill,” don’t count on it anytime soon.

That treadmill line came from a story in the Harvard Gazette, but to the school’s credit they did follow-up with the needed caveats:

“The path from these findings to a safe and effective medication may not be easy, and the findings will have to be replicated by other research groups, as well as refined, before they could lead to a clinical treatment.”

Opening up the black box of reprogramming cells. Researchers around the world have been turning adult cells into embryonic-like stem cells ever since Shinya Yamanaka’s Nobel-prize winning work showing it was possible more than six years ago. But no one really knew how it works. And that lack of understanding has made it quite difficult to improve on the poor efficiency and mixed-results of the process.

This led 30 senior scientists at eight institutions around the world to launch a project in 2010 to create an extremely detailed map of all the switching on and off of genes over time during the weeks it takes to reprogram adult cells to become “pluripotent” stem cells. The effort, called Project Grandiose, reported its results this week in a series of three papers in the journal Nature Communications. The name comes in part from the massive size of the data sets involved. Files could not be sent electronically. The teams were shipping memory storage devices around the world by courier. The leader of the project, Andras Nagy of Mount Sinai Hospital in Toronto described the project in a review of the field in Nature:

“It was the first high-resolution analysis of change in cell state over time. I’m not shy about saying grandiose.”

That journal review provides the best history of reprogramming that I have read and it is written on a level that a lay science hobbyist could understand. It gives a good explanation for one of the surprise findings from Project Grandiose that got a little over-played in some coverage. That was discovery of a new type of pluripotent stem cell called F Class, not referring to Mercedes car lines, but rather the fact that the cell clusters in a lab dish look fuzzy. The process that creates them in the lab seems to be more efficient than traditional reprogramming.

The critical output of the international project is more practical. Researchers around the world now have myriad new ways to think about improving the production of reprogrammed stem cells. Ken Zaret of the University of Pennsylvania, and a long time toiler in the field told the author of the Nature review this work opens up options for more reliable sources of cells to be used in human medicine:

“The motivation of my research is to treat patients. Anything that helps push iPS cells into the clinic excites me.”

Stem cells from inside the nose treat Parkinson’s in rats. A type of stem cell found in tissue that in humans would be thrown out after sinus surgery was retrieved from rats and then injected into the parts of their brains that do not function properly in Parkinson’s disease (PD). After 12 weeks the cells had migrated to where they were needed and matured into the type of nerve cell needed to cure PD and improved the function of the animals.

The cells, called inferior turbinate stem cells, could be a way to use a patient’s own stem cells as therapy for PD and avoid issues of immune rejection of donor cells, which may or may not be an issue in the brain, but this would remove a layer of risk. The work by a team at the University of Bielefeld and Dresden University of Technology in Germany was published in the journal Stem Cells Translational Medicine and the Houston Chronicle picked up the journal’s press release.

A time to kill, a time to heal: cells linked to aging also help heal wounds

Senescent cells, so called because of the role they play in the aging process, have acquired a bit of a bad reputation.

Yet new research from the Buck Institute suggests that these cells may not be so bad after all.

Buck Institute faculty Judith Campisi and Postdoc Marco Demaria. [Credit: The Buck Institute]

Buck Institute Professor Judith Campisi and Postdoc Marco Demaria. [Credit: The Buck Institute]

Reporting in today’s issue of Developmental Cell, Buck Institute scientists have found that, while senescent cells do indeed contribute to cellular aging and age-related diseases, they also play an important role in healing wounds. Furthermore, the team has identified the specific molecule in senescent cells that does the healing—pointing to a new therapy that could harness the good aspects of senescent cells, while flushing out the bad.

As we age, so do our cells. During cellular senescence, cells begin to lose their ability to grow and divide. The number of so-called senescent cells accumulates over time, releasing molecules thought to contribute to aging and age-related diseases such as arthritis and some forms of cancer.

But experiments led by Buck Institute Professor Judith Campisi and postdoctoral fellow Marco Demaria revealed that following a skin wound, cells that produce collagen and that line the blood vessels become senescent, and lose the ability to divide. Instead, they accelerate wound healing by secreting a growth factor called PDGF-AA. And once the wound was healed, the cells lost their senescence and shifted back into their normal state.

Because cellular senescence has long been linked to aging and age-related diseases, some research has been focused on finding ways to flush out senescent cells entirely. But the findings by the Buck Institute team throw a wrench in that idea, by revealing that these cells do in fact serve an important purpose.

According to Campisi, there is still a lot to learn:

“It is essential that we understand the full impact of senescence. The possibility of eliminating senescent cells holds great promise and is one of the most exciting avenues currently being explored in efforts to extend healthspan. This study shows that we can likely harness the positive aspects of senescence to ensure that future treatments truly do no harm.”

December ICOC Board Meeting to Begin Soon

The December ICOC Board Meeting begins this morning in Berkeley, CA.

The complete agenda can be found here. Dude to inclement weather our Spotlight on Disease has been canceled.

For those not able to attend, you are welcome to dial in:

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Finding the Sweet Spot: shifting metabolism keeps stem cells in suspended animation

The future is bright for a stem cell: it has the potential to become almost anything. This potential is one of its two defining characteristics. The second is that it can create copies of itself over and over again.

Researchers are announcing a new breakthrough on how best to keep embryonic stem cells (above) in a state of suspended animation.

Researchers are announcing a new breakthrough on how best to keep embryonic stem cells (above) in a state of suspended animation.

This second characteristic, known as the ability to self-renew, is of particular importance to researchers. After all, if they are to use stem cell technology to heal injury and treat disease, they must figure out how to keep them suspended in this embryonic state, so that large quantities can be grown in order to manufacture enough treatments for all who need them.

Unfortunately, that is easier said than done. But scientists have made extraordinary progress, developing a specific, nutrient-rich environment—a ‘medium’ called 2i—that can keep cells in a suspended, animation-like state.

The only problem was that they didn’t know why it worked.

Enter a joint team of scientists from The Rockefeller University and Memorial Sloan Kettering Cancer Center in New York, who today announce in the journal Nature that they may have cracked the case. According to team leader C. David Allis, it all comes down to the cell’s metabolism.

A cell’s metabolism is not unlike our body’s metabolism, though on a much smaller scale. Cellular metabolism refers to the process by which chemical reactions transform food into energy and other cellular products through something called the Citric Acid Cycle. The faster the cells’ metabolism, the faster the cycle produces energy, and vice versa.

Previously, scientists had observed a connection between the Citric Acid Cycle and the way in which a cell’s DNA was bundled into what is known as chromatin.

Embryonic stem cells (ES cells) have a different chromatin structure than mature, differentiated cells. This allows for heightened gene expression. [Credit: stembook.org]

Embryonic stem cells (ES cells) have a different chromatin structure than mature, differentiated cells. This allows for heightened gene expression. [Credit: stembook.org]

Chromatin is made by winding DNA strands around proteins called histones, much like winding strands of yarn around a tennis ball. The pattern in which DNA is organized into the chromatin structure is crucial: it affects which genes are switched on and off, and when.

For genes to become activated, or ‘expressed,’ they must be physically accessible within the chromatin structure. Postdoctoral researcher and co-first author Bryce Carey hypothesized that speeding up or slowing down a cell’s metabolism was responsible for which genes were accessible, and could therefore become activated. As he explained in a news release:

“What if, in stem cells, the changes to chromatin reflect a unique metabolism that helps to drive reactions that help to keep chromatin accessible? This connection would explain how embryonic stem cells are uniquely poised to activate so much of their genomes.”

To pinpoint the exact connection between metabolism and gene expression, Carey and co-first author Lydia Finley compared the metabolic functions of embryonic stem cells grown in the 2i medium and compared them to cells grown in a traditional medium made from bovine serum.

When study authors Bryce Carey (left) and Lydia Finley (right) exposed mouse embryonic stem cells to the metabolite alpha-ketoglutarate, those cells became more likely to renew themselves, appearing as pink colonies on the screen. This is one of the first demonstrations that a metabolite can influence the fate of stem cells. [Credit: Zach Veilleux / The Rockefeller University]

When study authors Bryce Carey (left) and Lydia Finley (right) exposed mouse embryonic stem cells to the metabolite alpha-ketoglutarate, those cells became more likely to renew themselves, appearing as pink colonies on the screen. This is one of the first demonstrations that a metabolite can influence the fate of stem cells. [Credit: Zach Veilleux / The Rockefeller University]

Surprisingly, the team found that the 2i cells were producing energy at staggering levels—through a molecular shortcut that cut out an entire step of the Citric Acid Cycle. This shortcut boosted the production of a protein called alpha-ketoglutarate, which in turn spurred more efficient energy production. It was as if the 2i medium instilled these embryonic stem cells with super powers.

Alpha-ketoglutarate appeared to be the key to shifting cells’ metabolism so that the right genes are expressed—thus keeping the cell in an embryonic state. Even cells growing in the traditional, bovine serum medium became supercharged when given a healthy dose of alpha-ketoglutarate.

These results not only solve a long-standing mystery of why the 2i medium was so superior for growing stem cells, they also pinpoint the particular protein—alpha-ketoglutarate—that is at the heart of this difference. This discovery, according to Allis, moves us closer to developing stem cell-based treatments in the clinic:

“This newly established link between metabolism and stem cell fate improves our understanding of development and regeneration, which may, in turn, bring us a little closer to harnessing stem cells’ ability to generate new tissue as a way to, for example, heal spinal cord injuries or cure Type 1 diabetes. It may also add a new dimension to our understanding of cancer, in which differentiated cells erroneously take on stem-cell like properties.”

Stem cells and professional sports: a call for more science and less speculation

In the world of professional sports, teams invest tens of millions of dollars in players. Those players are under intense pressure to show a return on that investment for the team, and that means playing as hard as possible for as long as possible. So it’s no surprise that players facing serious injuries will often turn to any treatment that might get them back in the game.

image courtesy Scientific American

image courtesy Scientific American

A new study published last week in 2014 World Stem Cell Report (we blogged about it here) highlighted how far some players will go to keep playing, saying at least 12 NFL players have undergone unproven stem cell treatments in the last five years. A session at the recent World Stem Cell Summit in San Antonio, Texas showed that football is not unique, that this is a trend in all professional sports.

Dr. Shane Shapiro, an orthopedic surgeon at the Mayo Clinic, says it was an article in the New York Times in 2009 about two of the NFL players named in the World Stem Cell Report that led him to becoming interested in stem cells. The article focused on two members of the Pittsburgh Steelers team who were able to overcome injuries and play in the Super Bowl after undergoing stem cell treatment, although there was no direct evidence the stem cells caused the improvement.

“The next day, the day after the article appeared, I had multiple patients in my office with copies of the New York Times asking if I could perform the same procedure on them.”

Dr. Shapiro had experienced what has since become one of the driving factors behind many people seeking stem cell therapies, even ones that are unproven; the media reports high profile athletes getting a treatment that seems to work leading many non-athletes to want the same.

“This is not just about high profile athletes it’s also about older patients, weekend warriors and all those with degenerative joint disease, which affects around 50 million Americans. Currently for a lot of these degenerative conditions we don’t have many good non- surgical options, basically physical therapy, gentle pain relievers or steroid injections. That’s it. We have to get somewhere where we have options to slow down this trend, to slow down the progression of these injuries and problems.”

Shapiro says one of the most popular stem cell-based approaches in sports medicine today is the use of plasma rich platelets or PRP. The idea behind it makes sense, at least in theory. Blood contains platelets that contain growth factors that have been shown to help tissue heal. So injecting a patient’s platelets into the injury site might speed recovery and, because it’s the patient’s own platelets, the treatment probably won’t cause any immune response or prove to be harmful.

That’s the theory. The problem is few well-designed clinical trials have been done to see if that’s actually the case. Shapiro talked about one relatively small, non-randomized study that used PRP and in a 14-month follow-up found that 83% of patients reported feeling satisfied with their pain relief. However, 84% of this group did not have any visible improved appearance on ultrasound.

He is now in the process of carrying out a clinical trial, approved by the Food and Drug Administration (FDA), using bone marrow aspirate concentrate (BMAC) cells harvested from the patient’s own bone marrow. Because those cells secrete growth factors such as cytokines and chemokines they hope they may have anti-inflammatory and regenerative properties. The cells will be injected into 25 patients, all of whom have arthritic knees. They hope to have results next year.

Dr. Paul Saenz is a sports medicine specialist and the team physician for the San Antonio Spurs, the current National Basketball Association champions. He says that sports teams are frequently criticized for allowing players to undergo unproven stem cell treatments but he says it’s unrealistic to expect teams to do clinical studies to see if these therapies work, that’s not their area of expertise. But he also says team physicians are very careful in what they are willing to try.

“As fervent as we are to help bring an athlete back to form, we are equally fervent in our desire not to harm a $10 million athlete. Sports physicians are very conservative and for them stem cells are never the first thing they try, they are options when other approaches have failed.”

Saenz said while there are not enough double blind, randomized controlled clinical trials he has seen many individual cases, anecdotal evidence, where the use of stem cells has made a big difference. He talked about one basketball player, a 13-year NBA veteran, who was experiencing pain and mobility problems with his knee. He put the player on a biologic regimen and performed a PRP procedure on the knee.

“What we saw over the next few years was decreased pain, and a dramatic decrease in his reliance on non-steroidal anti inflammatory drugs. We saw improved MRI findings, improved athletic performance with more time on court, more baskets and more rebounds.”

But Saenz acknowledges that for the field to advance anecdotal stories like this are not enough, well-designed clinical trials are needed. He says right now there is too much guesswork in treatments, that there is not even any agreement on best practices or standardized treatment protocols.

Dr. Shapiro says for too long the use of stem cells in sports medicine has been the realm of individual physicians or medical groups. That has to change:

“If we are ever to move forward on this it has to be opened up to the scientific community, we have to do the work, do the studies, complete the analysis, open it up to our peers, report it in a reputable journal. If we want to treat the 50 million Americans who need this kind of therapy we need to go through the FDA approval process. We can’t just continue to treat the one patient a month who can afford to pay for all this themselves. “