Stem cell stories that caught our eye: Cancer genetics, cell fate, super donors and tale of road to diabetes cure

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.

For cancer growth timing is everything. A study originating at the University of Southern California suggests tumors are born to be bad. Mutations constantly occur during the life of a tumor but those that occur early on determine if a tumor will grow as a benign mass of a cancerous one that spreads.

Describing the genetic markers the team found, the senior author, Christina Curtis, who recently moved to Stanford, was quoted in a story in ScienceBlog:

“What you see in the final cancer was there from the beginning.”

The CIRM funded team completed detailed genetic analysis of tumor cells surgically removed from colon cancer patients. Doctors treating these patients have long been hampered by an inability to tell which tumors will remain small and benign and which will develop into full-blown cancer. The researchers suggest the genetic fingerprints they have uncovered could lead to improved diagnosis for patients.

Physical forces also key to cell fate.
Putting the squeeze on stem cells may be what’s needed to get them to become bone. In this case, a team at the University of California, San Diego, used teeny tiny tweezers called “optical tweezers,” to trigger key internal signals that directed stem cells to go down the path to bone.

Pressure results in release of a cell signal shown in red

Pressure results in release of a cell signal shown in red

We have frequently written about the tremendous importance of a stem cell’s environment—its neighborhood if you will—in determining its fate. Yingxiao Wang, who led the study, described this role in a press release from the university picked up by ScienceNewsline:

“The mechanical environment around a stem cell helps govern a stem cell’s fate. Cells surrounded in stiff tissue such as the jaw, for example, have higher amounts of tension applied to them, and they can promote the production of harder tissues such as bone.”

He said the findings should help researchers trying to replicate the natural stem cell environment in the lab when they try to grow replacement tissues for patients.

Super donors could provide matching tissue.
One of the biggest challenges of using stem cells to replace damaged tissue is avoiding immune system rejection of the new cells. CIRM-grantee Cellular Dynamics International (CDI) announced this week that they have made key initial steps to creating a cell bank that could make this much easier.

Our bodies use molecules on the surface of our cells to identify tissue that is ours versus foreign such as bacteria. The huge variation in those molecules, called HLA, makes the matching needed for donor organ, or donor cells, more difficult than the New York Times Sunday crossword. But a few individuals posses an HLA combination that allows them to match to a large percent of the population.

CDI has now created clinical grade stem cell lines using iPS reprogramming of adult tissue from two such “super donors.” Just those two cell lines provide genetic matches for 19 percent of the population. The company plans to develop additional lines from other super donors with the goal of creating a bank that would cover 95 percent of the population.

Reuters picked up the company’s press release. CIRM does not fund this project, but we do fund another cell bank for which CDI is creating cells to better understand the causes of 11 diseases that have complex genetic origins

Narrative tells the tale of developing diabetes therapy. MIT Technology Review has published a well-told feature about the long road to creating a stem cell-based therapy for diabetes. Author Bran Alexander starts with the early days of the “stem cell wars” and carries the tale through treatment of the first patients in the CIRM-funded clinical trial being carried out by ViaCyte and the University of California, San Diego.

The piece quotes Viacyte’s chief scientific officer Kevin D’Amour about the long road:

“When I first came to ViaCyte 12 years ago, cell replacement through stem cells was so obvious. We all said, ‘Oh, that’s the low-hanging fruit.’ But it turned out to be a coconut, not an apple.”

But the article shows that with Viacyte’s product as well as others coming down the pike, that coconut has been cracked and real hope for diabetics lies inside.

Stem cell stories that caught our eye: repairing radiation damage, beta thalassemia clinical trial and disease models

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 repair brain damage from radiation therapy. Radiation for brain cancer can be a lifesaver but it can also be a dramatic life changer. If often leaves patients with considerably reduced brain function. Now a team at New York’s Memorial Sloan Kettering Cancer Center has found a way to instruct human stem cells to repair some of that damage—at least in rats.

The damage seems to be to the middle-man or so-called progenitor cells that maintain the myelin cells that insulate the nerves in the brain. When that myelin is damaged by the radiation those progenitor cells are no longer able to make repairs and that results in reduced nerve function. Rats given the stem cells regained both cognitive and motor skills lost after brain radiation.

The team leader, Viviane Taber, noted this work could make radiation therapy even more of a lifesaver. ScienceDaily quoted Tabar from materials provided by Cell Press that published the work:

“This will have to be proven further, but if we can repair the brain effectively, we could be bolder with our radiation dosing, within limits.”

This could be especially important in children, for whom physicians deliberately deliver lower radiation doses.


Stem cell trial for Beta-Thalassemia cleared to begin.
CIRM-grantee Sangamo BioSciences announced this week that the Food and Drug Administration (FDA) had accepted its application to begin a clinical trial using genetically edited stem cells to treat patients with beta-thalassemia. This trial, in patients who require regular blood transfusions to survive, is the ninth CIRM-funded clinical trail to gain clearance from the FDA.

Other clinical trials have used genetically modified stem cells, but they have used various techniques to add a correct gene or silence an unwanted gene. This will be the first clinical trial using one of the newer techniques that actually goes into a person’s genes and edits them to correct a disease. We wrote about this beta-thalassemia project here.

The Sacramento Business Times picked up the company’s press release that quoted Sangamo president Edward Lanphier on the company’s goal, “the aim of providing transfusion-dependent beta-thalassemia patients with a one-time treatment for this devastating disease.”

Disease modeling for science wonks. Vivien Marx wrote a feature article for Nature Methods that provides the most thorough review of the use of reprogramed iPS-type stem cells as disease models that I have read. In particular she discusses the power of using new gene editing tools to modify the cells so that when they mature into adult tissues they will display specific disease traits.

Svendsen hopes to use gene-edited iPS type stem cells to fully understand neurodegenerative diseases

Svendsen hopes to use gene-edited iPS type stem cells to fully understand neurodegenerative diseases

She starts with a narrative about CIRM-grantee Clive Svendsen’s work to understand spinal muscular atropohy (SMA) when he was in Wisconsin and to understand amyotrophic lateral sclerosis (ALS) now at Cedars Sinai in Los Angeles. She goes on to show just how powerful these gene-edited stem cells can be, but also how difficult it is to use the technology in a way that generates useful information. Marx is a strong science journalist, who for many years has shown a skill at explaining complex technologies.

She also discusses the various iPS cell banks developed around the world including CIRM’s cell bank and the value of having non-gene-edited cells from patients that naturally show the disease traits.

Thorough review of changes at CIRM.
Alex Lash at xconomy wrote an in-depth overview of our president Randy Mills’ plans for the next phase of our agency that Randy calls CIRM 2.0. Calling the plans an extensive “renovation” Lash described the portions of the new structure that were already in place and listed the ones set to come online in the next six months.

As a balanced journalist he runs through some of the highs and lows of our public perception during the initial phase of the agency and then discusses the new tone set by Mills:

“CIRM is less a grant-making government agency than a ‘discerning investor’ that’s going to be ‘as creative and innovative’ as possible in getting treatments approved, Mills says. ‘We have no mission above accelerating stem cell therapies to patients.’ ”

Stem cell stories that caught our eye: new ways to reprogram, shifting attitudes on tissue donation, and hockey legend’s miracle questioned

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 produced from skin. Starting with human skin cells a team at the University of Iowa has created iPS-type stem cells through genetic reprogramming and matured those stem cells into insulin-producing cells that successfully brought blood-sugar levels closer to normal when transplanted in mice.

University of Iowa researchers reprogrammed human skin cells to create iPS cells, which were then differentiated in a stepwise fashion to create insulin-producing cells. When these cells were transplanted into diabetic mice, the cells secreted insulin and reduced the blood sugar levels of the mice to normal or near-normal levels. The image shows the insulin-producing cells (right) and precursor cells (left). [Credit: University of Iowa]

University of Iowa researchers reprogrammed human skin cells to create iPS cells, which were then differentiated in a stepwise fashion to create insulin-producing cells. When these cells were transplanted into diabetic mice, the cells secreted insulin and reduced the blood sugar levels of the mice to normal or near-normal levels. The image shows the insulin-producing cells (right) and precursor cells (left).
[Credit: University of Iowa]

The cells did not completely restore blood-sugar levels to normal, but did point to the possibility of achieving that goal in the future, something the team leader Nicholas Zavazava noted in an article in the Des Moines Register, calling the work an “encouraging first step” toward a potential cure for diabetes.

The Register discussed the possibility of making personalized cells that match the genetics of the patient and avoiding the need for immune suppression. This has long been a goal with iPS cells, but increasingly the research community has turned to looking for options that would avoid immune rejection with donor cells that could be off-the-shelf and less expensive than making new cells for each patient.

Heart cells from reprogramming work in mice. Like several other teams, a group in Japan created beating heart cells from iPS-type stem cells. But they went the additional step of growing them into sheets of heart muscle that when transplanted into mice integrated into the animals own heart and beat to the same rhythm.

The team published the work in Cell Transplantation and the news agency AlianzaNews ran a story noting that it has previously been unclear if these cells would get in sync with the host heart muscle. The result provides hope this could be a route to repair hearts damaged by heart attack.

Patient attitudes on donating tissue. A University of Michigan study suggests most folks don’t care how you use body tissue they donate for research if you ask them about research generically. But their attitudes change when you ask about specific research, with positive responses increasing for only one type of research: stem cell research.

On the generic question, 69 percent said go for it, but when you mentioned the possibility of abortion research more than half said no and if told the cells might lead to commercial products 45 percent said nix. The team published their work in the Journal of the American Medical Association and HealthCanal picked up the university’s press release that quoted the lead researcher, Tom Tomlinson, on why paying attention to donor preference is so critical:

“Biobanks are becoming more and more important to health research, so it’s important to understand these concerns and how transparent these facilities need to be in the research they support.”

CIRM has begun building a bank of iPS-type stem cells made from tissue donated by people with one of 11 diseases. We went through a very detailed process to develop uniform informed consent forms to make sure the donors for our cell bank knew exactly how their cells could be used. Read more about the consent process here.

Mainstream media start to question hockey legend’s miracle. Finally some healthy skepticism has arrived. Hockey legend Gordie Howe’s recovery from a pair of strokes just before the holidays was treated by the general media as a true Christmas miracle. The scientific press tried to layer the coverage with some questions of what we don’t know about his case but not the mainstream media. The one exception I saw was Brad Fikes in the San Diego Union Tribune who had to rely on a couple of scientists who were openly speaking out at the time. We wrote about their concerns then as well.

Now two major outlets have raised questions in long pieces back-to-back yesterday and this morning. The Star in hockey-crazed Canada wrote the first piece and New York Magazine wrote today’s. Both raise serious questions about whether stem cells could have been the cause of Howe’s recovery and are valuable additions to the coverage.

Stem cell stories that caught our eye: Heart self-repair, MS therapy and genetic screening

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.

Uncovering mystery of heart self-repair. We have often written about work that tries to get the body’s self-healing mechanisms to do a better job. This is particularly desirable but difficult in heart injury. A CIRM-funded team as Children’s Hospital Los Angeles found some clues to achieving this goal by investigating critters good at it. Neonatal mice have an amazing capacity to repair heart damage for about the first seven days of their life.

A young mouse heart with resting heart muscle cells (red) and proliferating muscle cells (green)

A young mouse heart with resting heart muscle cells (red) and proliferating muscle cells (green)

The team looked at what genetic and molecular systems were active during the period of repair and not active at other times. Senior author of the study, Ellen Lien, described the importance of what they are finding in a press release picked up by ScienceCodex:

“Using models such as zebrafish and neonatal mice that regenerate their hearts naturally, we can begin to identify important molecules that enhance heart repair.”

Good news on MS needed many caveats. Some good news on using stem cell transplants for Multiple Sclerosis published in the Journal of the American Medical Association this week sparked a flurry of news reports. But most of those stories lacked the caveats the study required and generated several calls to our office from desperate patients wanting to try the therapy. HealthDay did a good job of pointing out the hope and the limitations of the therapy and of the clinical trial itself.

Only half of the patients responded, which is still good for what can be such an intractable disease. But, only one subset of patients showed the benefit; ones earlier in the course of the disease with the form known as relapsing-remitting MS. None of the later stage patients responded, which makes some sense because if the transplant is altering the immune system, it would have the most impact when the patient’s immune cells are most actively attacking their nerves.

A personal tale of using genetic screening of embryos. Over the past couple years researchers’ need for new embryonic stem cell lines has declined. As a result, many of the new cell lines registered with the National Institutes of Health in the past year have been ones carrying specific genetic disease traits that have been screened out of consideration by couples using pre-implant genetic diagnosis (PGD) for family planning at in vitro fertilization clinics.

While we have written about this conceptually a feature story posted by the University of Michigan and picked up by ScienceDaily makes it very real through a family’s personal story. A devastating nerve disease called ALD runs in the prospective mother’s family so they decided to use PGD to avoid having a child with the disease, but they took it one step further. They donated the left over embryos that carried the genetic flaw to the university for research. Now they are about to celebrate the first birthday of a healthy son and the researchers have a valuable research tool as one stem cell scientist at the University, Gary Smith, explained:

“Disease-specific human embryonic stem cells are the gold standard for research —the purest pathway to understanding disease establishment and progression, and to discovering ways to prevent or alleviate pain and suffering caused by these diseases.”

UC Davis Surgeons Begin Clinical Trial that Tests New Way to Deliver Stem Cells; Heal Bone Fractures

Each year, approximately 8.9 million people worldwide will suffer a bone fracture. Many of these fractures heal with the help of traditional methods, but for some, the road to recovery is far more difficult.

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After exhausting traditional treatments—such as surgically implanted pins or plates, bed rest and injections to spur bone growth—these patients can undergo a special type of stem cell transplant that directs stem cells extracted from the bone marrow to the fracture site to speed healing.

This procedure has its drawbacks, however. For example, the act of extracting cells from one’s own bone marrow and then injecting them into the fracture site requires two very painful surgical procedures: one to extract the cells, and another to implant them. Recovery times for each procedure, especially in older patients, can be significant.

Enter a team of surgeons at UC Davis. Who last week announced a ‘proof-of-concept’ clinical trial to test a device that can extract and isolate stem cells far more efficiently than before—and allow surgeons to implant the cells into the fracture in just a single surgery.

As described in HealthCanal, he procedure makes use of a reamer-irrigator-aspirator system, or RIA, that normally processes wastewater during bone drilling surgery. As its name implies, this wastewater was thought to be useless. But recent research has revealed that it is chock-full of stem cells.

The problem was that the stem cells were so diluted within the wastewater that they couldn’t be used. Luckily, a device recently developed by Sacramento-based SynGen, Inc., was able to quickly and efficiently extract the cells in high-enough concentrations to then be implanted into the patient. Instead of having to undergo two procedures—the patient now only has to undergo one.

“The device’s small size and rapid capabilities allow autologous stem cell transplantation to take place during a single operation in the operation room rather than requiring two procedures separated over a period of weeks,” said UC Davis surgeon Mark Lee, who is leading the clinical trial. “This is a dramatic difference that promises to make a real impact on healing and patient recovery.”

Hear more from Lee about how stem cells can be used to heal bone fractures in our 2012 Spotlight on Disease.

Stem cell stories that caught our eye: EU approves a cell therapy, second ALS treatment shows promise and new gut cells work

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.

Europe approves first 2nd generation stem cell therapy.
While blood stem cells in bone marrow have been used to treat patients with certain blood cancers for more than 40 years, it has been a long wait for other uses of stem cells to gain official nods from regulatory bodies. The first came in 2012 when Canada approved Prochymal a stem cell therapy for kids who have a severe immune reaction after bone marrow transplant for cancer. That therapy helps the patients regulate their immune response and can be life saving.

Now the European Medicines Agency has approved a therapy for repairing eyes with damaged corneas—the first of a new generation of stem cell therapies that replace or repair specific tissues. The therapy uses a type of stem cell found in the eye called a limbal stem cell. An Italian team pioneered the procedure that has successfully restored vision to scores of patients whose eyes were damaged by chemicals or burns. An official with the EMA noted the significance of this approval in an agency press release.

“This recommendation represents a major step forward in delivering new and innovative medicines to patients.”

The BBC broke the news with a brief story, and MSN followed up with a bit more detail. (And no, this did not happen “this week” but it did happen after we went dark for the holidays.) CIRM also funds work with limbal stem cells.

Second type of stem cells shows benefit for ALS patients. Over the past couple years we have been writing about positive early trial results from Neuralstem for its therapy using a nerve stem cell for treating patients with ALS, also called Lou Gehrig’s disease. This week the company Brainstorm reported data showing improvement in most of the patients treated with a type of stem cell found in bone marrow and fat, mesenchymal stem cells.

The Neuralstem trials used donor stem cells and the Brainstorm trial uses a patient’s own cells, hence the drug name NeuOwn. But they have be revved up in the lab so that they secrete large quantities of what are called neurotrophic factors, chemicals that seem to protect nerves from damage by the disease and potentially foster healing of already damaged nerves.

Eleven of 12 patients experienced a decrease in the rate of progression of this normally very aggressive disease. The Israeli company completed its early trials in Israel but began a second stage trial at Massachusetts General Hospital in April. Reuters ran a story about the announcement.

New intestine engineered from stem cells. CIRM-grantee Tracy Grikscheit has previously reported growing tissues that look like intestinal cells and that have all the right cellular dog tags of our guts. Today the university announced she has shown she can grow tissues that actually function like our guts. They can absorb life-sustaining nutrients.

Because her work focuses on the devastating condition that results when a baby is born with insufficient intestine, it was not surprising this morning to find a good story about her work on the web site MotherBoard. The site quotes her on the latest advance:

“What’s important about this study is it’s not just taking pictures of the cells and saying ok, they’re in the proper location. We’re actually also looking at the function, so we’re showing that not only are the cells present that would for example absorb the sugar in your breakfast, but they actually are doing that job of absorbing sugar.”

Grikscheit works at Children’s Hospital Los Angeles and you can read about her CIRM-funded work to build new intestine here.


Luck’s role in stem cell mutations key to cancer.
Most of the popular talk about risk and cancer centers on inheriting bad genes and being exposed to nasty chemicals in our daily lives. But a new study says the biggest risk is more akin to a roulette wheel.

A study published in Science by a team at Johns Hopkins looked at 31 types of tissue in our bodies and found that random mutations that occur while our tissue-specific stem cells divide correlates better with cancer risk than what we inherit or environmental risks combined. The Scientist produced one of the more thoughtful pieces of the many on the research that appeared in the media this week.

A personal story about getting into stem cell research. I enjoy hearing about how people get into this fascinating field and the media team at the University of Southern California has provided a good example. They profile recent recruit, Michael Bonaguidi who explains how he made the switch from physical to biological science:

“Growing up on Legos and Lincoln Logs, I was very fascinated with building things. As I took more biology courses and was exposed to other facets of science — from chemistry to physics — I became more interested not in the outside but within. And that’s what got me into bioengineering versus structural engineering.”

Described as shaping brains instead of cities he is looking for the types of cells that can rebuild the brain after injury or stroke. HealthCanal picked up the university’s feature.

Stem Cell Stories that Caught Your Eye: The Most Popular Stem Cellar Stories of 2014

2014 marked an extraordinary year for regenerative medicine and for CIRM. We welcomed a new president, several of our research programs have moved into clinical trials—and our goal of accelerating treatments for patients in need is within our grasp.

As we look back we’d like to revisit The Stem Cellar’s ten most popular stories of 2014. We hope you enjoyed reading them as much as we did reporting them. And from all of us here at the Stem Cell Agency we wish you a Happy Holidays and New Year.

10. UCSD Team Launches CIRM-Funded Trial to Test Safety of New Leukemia Drug

9. Creating a Genetic Model for Autism, with a Little Help from the Tooth Fairy

8. A Tumor’s Trojan Horse: CIRM Researchers Build Nanoparticles to Infiltrate Hard-to-Reach Tumors

7. CIRM funded therapy for type 1 diabetes gets FDA approval for clinical trial

6. New Videos: Living with Crohn’s Disease and Working Towards a Stem Cell Therapy

5. Creativity Program Students Reach New Heights with Stem Cell-Themed Rendition of “Let it Go”

4. Scientists Reach Yet Another Milestone towards Treating Type 1 Diabetes

3. Meet the Stem Cell Agency President C. Randal Mills

2. Truth or Consequences: how to spot a liar and what to do once you catch them

1. UCLA team cures infants of often-fatal “bubble baby” disease by inserting gene in their stem cells; sickle cell disease is next target

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.

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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.

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. “

World Stem Cell Summit: The environment stem cells find themselves in after transplant really matters

On Friday’s closing day of the 2014 World Stem Cell Summit a panel of three researchers working on neurodegenerative diseases drove home the importance of paying attention to the environment that surrounds stem cells after transplant.

world-stem-cells-summit-2014

CIRM grantee Evan Snyder from the Sanford-Burnham Institute noted that most of the neurologic diseases people are looking at are conditions associated with aging and the cellular makeup of the brain changes as we get older, adding that most of the diseases result from chronic states that have existed over many years. He contrasted this against mouse models of the disease, which usually involve artificially recreating the disease and treating shortly after the injury happens.

“In stem cell therapies there is a dialogue between the transplanted cells and the recipient. The host influences the fate of the stem cells.”

He noted that the patients we will be treating have generally had long-term degeneration and asked if we might be able to develop drugs that effect the environment where the stem cells will be placed so that it mimics more closely the environment found in the animal model in the acute phase, that is right after injury.

One aspect of the environment in the brain in most patients with neurodegeneration is chronic inflammation. Another CIRM grantee on the panel, Jeanne Loring of the Scripps Research Institute, discussed a project her team hopes will take advantage of the inflammation that occurs in Alzheimer’s disease. They are loading nerve stem cells with an enzyme that can degrade the plaque that accumulates in nerves in the disease. Because stem cells home to inflammation, they hypothesize that the stem cells will be drawn to deliver their cargo to the nerves with the worst plaque.

The third panelist, Erzi Kokovay of the University of Texas Health Science Center in San Antonio, described the changes in the brain as we age in a bit more detail. She described infiltration of cells called microglia that researchers will need to take into account when they plan to transplant stem cells in the brain.

While on the surface this all may sound like another road block to getting to the stem cell cures we all want, the presentation actually made me optimistic that we are starting to learn enough about the field that we are more likely to get it right when we start to treat some of these devastating brain diseases.

Don Gibbons