Stem cell stories that caught our eye: heart disease, premature infants and incontinence

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.

Decoding heart health and genetics in Asians. A study from CIRM grantee Joseph Wu at Stanford may point the way to using stem cells to solve problems caused by too many drugs being tested predominantly on white males. Ethnic variations to drug response too often get ignored in current clinical trials.

The Stanford team has used iPS type stem cells to create a disease-in-a-dish model of a genetic mutation that effects 500 million people, but mostly East Asians. The mutation disables the metabolic protein called ALDH2 and results in increased risk of heart disease and increases the risk of death after a heart attack. By growing heart muscle from stem cells made from the skin of patients with the mutation his team found that the defect alters the way the heart cells react to stress.

Wu suggests that drug companies one day may keep banks of iPS cells from various ethnic groups to see how their responses to drugs differ. Science Daily ran the university’s press release.

Stem cells may treat gut disease in premies.
A laundry list of medical challenges confronts premature babies, but few are as deadly as the intestinal disease that goes by the name NEC, or necrotizing enterocolitis. It strikes with no notice and can kill within hours.

140925100256-largeA team at the University of Ohio reports they have developed what may be a two-pronged attack on the disease. First, they found a biomarker that can predict which infants might develop NEC, and second they have tested stem cells for treating the intestinal damage done by the disease. In an animal model they found that a type of stem cell found in bone marrow, mesenchymal stem cells, can reduce the inflammation that causes the damage and that neural stem cells can repair the nerve connections disrupted by the inflammation.

While this explanation sounds straight forward, getting to that potential intervention was anything but a simple path. The university wrote an extensive feature detailing the many years and many steps the research team took to unravel this who-done-it that involves the gut’s extensive “brain” and immune system. Science Daily picked up the piece.

We recently posted a video about a project we fund using stem cells to develop a treatment for irritable bowel disease.

Fat stem cells tested in incontinence. For far too many older women laughing and coughing can lead to embarrassing bladder leaks. Several groups are working with various types of stem cells to try to strengthen the urinary sphincter and help patients lead a more normal life. A team at Cleveland Clinic now reports some positive results using the most easily accessed form of stem cells, those in fat.

They harvested patients’ own fat stems cells, grew them in the lab for three weeks and then mixed them with a collagen gel from cows to hold them in place before injecting them into the sphincter. Three of five patients passed “the cough test” after one year. Good results, but clearly more work needs to be done to yield more uniform results. Stem Cells Translational Medicine published the research and issued this press release.

Some researcher suspect starting with an earlier stage, more versatile stem cell might yield better results. One of our grantees is developing cells to treat incontinence starting with reprogrammed iPS type stem cells.

New course looks at where fact and fiction overlap. I am a big fan of almost any effort to blend science and the arts. A professor at the University of Southern California seems to agree. CIRM grantee Gage Crump will be teaching a course next spring about science fiction and stem cells.

The university says the course, Stem Cells: Fact and Fiction, will range from babies born with three biological parents to regrown body parts. The course will explore the current state of stem cell biology as it closes the gap between reality and the sci fi visions of authors such as Margaret Atwood and Philip K. Dick. Crump describes it as:

“a mad scientist type of course, where we go through some real science but also [think] about what’s the future of science.”

Don Gibbons

Stem cell stories that caught our eye: first iPS clinical trial, cancer metabolism and magnates helping heal hearts

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.

First clinical trial with reprogrammed stem cells.
Today, a Japanese woman became the first patient to be treated with cells derived from reprogrammed iPS-type stem cells. The patient received cells matured into a type of cell damaged in the most common form of blindness, age-related macular degeneration.

Those cells, a normal part of the eye’s retina, were made from stem cells created from a skin sample donated by the patient several months ago. In the intervening time the resulting retinal cells have been tested in mice and monkeys to make sure they will not cause tumors. Because the cells have the same genes as the patient, researchers believe they may not be rejected by the patient’s immune system in the absence of immune suppressive drugs—the beauty of iPS technology.

Right now, that technology is much too cumbersome and time consuming to result in a broadly applicable therapy. But if this first clinical trial proves the immune system get-out-of-jail-free theory, it should intensify efforts to make iPS technology more efficient.

When Japanese authorities gave permission to treat the first patient earlier this week Popular Science provided an easy read version of the story and Nature News provided a bit more detail.

Cancer cells don’t handle their sugar well. Sugar has a bad rep these days. Now, it looks like manipulating sugar metabolism might lead to ways to better treat leukemia and perhaps, make therapies less toxic to normal cells. It turns out cancer cells are much more sensitive to changes in sugar level than normal blood stem cells or the intermediate cells that give rise the various branches of the blood system.

David Scadden at the Harvard Stem Cell Institute has long studied the role of the stem cell's environment in its function.

David Scadden at the Harvard Stem Cell Institute has long studied the role of the stem cell’s environment in its function.

A team led by old friend and colleague at the Harvard Stem Cell Institute, David Scadden, first looked at sugar metabolism in normal blood forming stem cells and their intermediate cells. They found that the parent stem cell and their direct offspring, those intermediate cells, behave differently when faced with various manipulations in sugar level, which makes sense since the intermediate cells are usually much more actively dividing.

But when they manipulated the genes of both types of cells to make them turn cancerous, the cancer cells from both were much more sensitive to changes in sugar metabolism. In a university press release picked up by ScienceCodex David said he hoped to interest drug companies in developing ways to exploit these differences to create better therapies.

Magnets and nanoparticles steer stem cells.
Getting stem cells to where they are needed to make a repair, and keeping them there is a major challenge. A team at Los Angeles’ Cedars-Sinai hospital that we fund (but not for this study) has taken an approach to this problem that is the equivalent of holding your pants up with a double set of button, a belt and suspenders.

Treating damaged hearts in rats they first loaded iron-containing nanoparticles with two types of antibodies, one that recognizes and homes to injured heart tissue and one that attracts healing stem cells. After infusing them into the animal’s blood stream, they placed a magnet over its heart to hold the iron nanoparticles near by. The iron provided the added benefit of letting the team track the cells via magnetic resonance imaging (MRI) to verify they did get to and stay where they were needed.

In a press release from the hospital picked up by ScienceDaily the lead researcher Eduardo Marban said:

“The result is a kind of molecular matchmaking,”

The study was published in Nature Communications and you can read about other work we fund in Marban’s lab trying to figure out once you get the stem cells to the heart exactly how do they create the repair.

Reprogrammed stem cells turned into white blood cells. We have written often about the difficulties of getting stem cells to create fully mature blood cells. Last week we talked about a Wisconsin team breaking the barrier for red blood cells. Now, a team at the Salk Institute is reporting success for white blood cells.

Starting with iPS-type stem cells they got the mature white cells via a two-step process. First they manipulated one gene called Sox2 to get the stem cells to become the right intermediate cells. Then they used a gene-regulating molecule called a micro-RNA to get the middleman cells to mature into white blood cells.

In a press release from the Salk, lead researcher Juan Carlos Izpisua Belmonte noted the clinical importance of the work:

“In terms of potential clinical applications, the hematopoietic system represents one of the most suitable tissues for stem cell-based therapies. . .”

The team published the research in the journal Stem Cells and the web portal BioSpace picked up the release.

Book on early spinal cord injury clinical trial. The title of a book on the first ever clinical trial using cells from embryonic stem cells kind of says it all: Inevitable Collision: The Inspiring Story that Brought Stem Cell Research to Conservative America.

Katy Sharify's experience in the first embryonic stem cell trial is featured in a new book and she discussed it in a video from a CIRM workshop.

Katy Sharify’s experience in the first embryonic stem cell trial is featured in a new book and she discussed it in a video from a CIRM workshop.


The book details the personal stories of the first and fifth patients in the spinal cord injury trial conducted by Geron. That company made the financial decision to end its stem cell product development in favor of its cancer products. But the spinal cord injury trial is now set to restart, modified to treat neck injuries instead of back injuries and at higher doses, through CIRM funding to the company that bought the Geron stem cell business, Asterias.

In a press release from the publisher, the book’s author explained her goal:

“Through this book I hope to bridge the gap between science and religion and raise awareness of the importance and power of stem cell research.”

The fifth patient in the Geron study, Katie Sharify, is featured in our “Stories of Hope” that have filled The Stem Cellar this week.

Don Gibbons

Stem Cell Stories that Caught our Eye: What’s the Best Way to Treat Deadly Cancer, Destroying Red Blood Cells’ Barricade, Profile of CIRM Scientist Denis Evseenko

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 vs. Drugs for Treating Deadly Cancer. When dealing with a potentially deadly form of cancer, choosing the right treatment is critical. But what if that treatment also poses risks, especially for older patients? Could advances in drug development render risky treatments, such as transplants, obsolete?

That was the focus of a pair of studies published this week in the New England Journal of Medicine, where a joint Israeli-Italian research team investigated the comparative benefits of two different treatments for a form of cancer called multiple myeloma.

Multiple myeloma attacks the body’s white blood cells. While rare, it is one of the most deadly forms of cancer—more than half of those diagnosed with the disease do not survive five years after being diagnosed. The standard form of treatment is usually a stem cell transplant, but with newer and better drugs coming on the market, could they render transplants unnecessary?

In the twin studies, the research team divided multiple myeloma patients into two groups. One received a combination of stem cell transplant and chemotherapy, while the other received a combination of drugs including melphalan, prednisone and lenalidmomide. After tracking these patients over a period of four years, the research team saw a clear advantage for those patients that had received the transplant-chemotherapy treatment combination.

To read more about these twin studies check out recent coverage in NewsMaxHealth.

Breaking Blood Cells’ Barricade. The process whereby stem cells mature into red blood cells is, unfortunately, not as fast as scientists would like. In fact, there is a naturally occurring barrier that keeps the production relatively slow. In a healthy person this is not necessarily a problem, but for someone in desperate need of red blood cells—it can prove to be very dangerous.

Luckily, scientists at the University of Wisconsin-Madison have found a way to break through this barrier by switching off two key proteins. Once firmly in the ‘off’ position, the team could boost the production of red blood cells.

These findings, published in the journal Blood, are critical in the context of disease anemia, where the patient’s red blood cell count is low. They also may lead to easier methods of stocking blood banks.

Read more about this exciting discovery at HealthCanal.

CIRM Scientist on the Front Lines of Cancer. Finally, HealthCanal has an enlightening profile of Dr. Denis Evseenko, a stem cell scientist and CIRM grantee from the University of California, Los Angeles (UCLA).

Born in Russia, the profile highlights Evseenko’s passion for studying embryonic stem cells—and their potential for curing currently incurable diseases. As he explains in the article:

“I had a noble vision to develop progressive therapies for the patient. It was a very practical vision too, because I realized how limited therapeutic opportunities could be for the basic scientist, and I had seen many great potential discoveries die out before they ever reached the clinic. Could I help to create the bridge between stem cells, research and actual therapeutics?”

Upon arriving at UCLA, Evseenko knew he wanted to focus this passion into the study of degenerative diseases and diseases related to aging, such as cancer. His bold vision of bridging the gap between basic and translational research has earned him support not only from CIRM, but also the National Institutes of Health and the US Department of Defense, among others. Says Evseenko:

“It’s my hope that we can translate the research we do and discoveries we make here to the clinic to directly impact patient care.”

Stem Cell Stories that Caught our Eye: A Zebrafish’s Stripes, Stem Cell Sound Waves and the Dangers of Stem Cell Tourism

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.

The zebrafish (Danio rerio) owes its name to a repeating pattern of blue stripes alternating with golden stripes. [Credit: MPI f. Developmental Biology/ P. Malhawar]

The zebrafish (Danio rerio) owes its name to a repeating pattern of blue stripes alternating with golden stripes. [Credit: MPI f. Developmental Biology/ P. Malhawar]

How the Zebrafish Got its Stripes. Scientists in Germany have identified the different pigment cells that emerge during embryonic development and that determine the signature-striped pattern on the skins of zebrafish—one of science’s most commonly studied model organisms. These results, published this week in the journal Science, will help researchers understand how patterns, from stripes to spots to everything in between, develop.

In the study, scientists at the Max Planck Institute for Developmental Biology mapped how three distinct pigment cells, called black cells, reflective silvery cells, and yellow cells emerge during development and arrange themselves into the characteristic stripes. While researchers knew these three cell types were involved in stripe formation, what they discovered here was that these cells form when the zebrafish is a mere embryo.

“We were surprised to observe such cell behaviors, as these were totally unexpected from what we knew about color pattern formation”, says Prateek Mahalwar, first author of the study, in a news release.

What most surprised the research team, according to the news release, was that the three cell types each travel across the embryo to form the skin from a different direction. According to Dr. Christiane Nüsslein-Volhard, the study’s senior author:

“These findings inform our way of thinking about color pattern formation in other fish, but also in animals which are not accessible to direct observation during development such as peacocks, tigers and zebras.”

Sound Waves Dispense Individual Stem Cells. It happens all the time in the lab: scientists need to isolate and study a single stem cell. The trick is, how best to do it. Many methods have been developed to achieve this goal, but now scientists at the Regenerative Medicine Institute (REMEDI) at NUI Galway and Irish start-up Poly-Pico Technologies Ltd. have pioneered the idea of using sound waves to isolate living stem cells, in this case from bone marrow, with what they call the Poly-Pico micro-drop dispensing device.

Poly-Pico Technologies Ltd., a start-up that was spun out from the University of Limerick in Ireland, has developed a device that uses sound energy to accurately dispense protein, antibodies and DNA at very low volumes. In this study, REMEDI scientists harnessed this same technology to dispense stem cells.

These results, while preliminary, could help improve our understanding of stem cell biology, as well as a number of additional applications. As Poly-Pico CEO Alan Crean commented in a news release:

“We are delighted to see this new technology opportunity emerge at the interface between biology and engineering. There are other exciting applications of Poly-Pico’s unique technology in, for example, drug screening and DNA amplification. Our objective here is to make our technology available to companies, and researchers, and add value to what they are doing. This is one example of such a success.”

The Dangers of Stem Cell Toursim. Finally, a story from ABC News Australia, in which they recount a woman’s terrifying encounter with an unproven stem cell technique.

In this story, Annie Levington, who has suffered from multiple scleoris (MS) since 2007, tells of her journey from Melbourne to Germany. She describes a frightening experience in which she paid $15,000 to have a stem cell transplant. But when she returned home to Australia, she saw no improvement in her MS—a neuroinflammatory disease that causes nerve cells to whither.

“They said I would feel the effects within the next three weeks to a year. And nothing – I had noticed nothing whatsoever. [My neurologist] sent me to a hematologist who checked my bloods and concluded there was no evidence whatsoever that I received a stem cell transplant.”

Sadly, Levington’s story is not unusual, though it is not as dreadful as other instances, in which patients have traveled thousands of miles to have treatments that not only don’t cure they condition—they actually cause deadly harm.

The reason that these unproven techniques are even being administered is based on a medical loophole that allows doctors to treat patients, both in Australia and overseas, with their own stem cells—even if that treatment is unsafe or unproven.

And while there have been some extreme cases of death or severe injury because of these treatments, experts warn that the most likely outcome of these untested treatments is similar to Levington’s—your health won’t improve, but your bank account will have dwindled.

Want to learn more about the dangers of stem cell tourism? Check out our Stem Cell Tourism Fact Sheet.

Stem cell stories that caught our eye: Willie Nelson’s contribution to muscular dystrophy, cell fate maps and funding

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.

Cell fate map can show quality of cells.
The phrase “there is more than one way to skin a cat” fits much of science. It is quite true for using stem cell science to generate a needed type of adult cell to repair damaged tissue. The most traditional way, directing early stem cells, the ones called pluripotent, to mature into the desired tissue is often cumbersome and has the potential of leaving behind a few of those early cells that could cause a tumor. More recently, many teams have been starting with one type of adult tissue and reprogramming them to directly convert into a different adult tissue without passing through that potentially tumor causing state. But we have not had a good way to measure which route produces the higher quality cells—which one yield cells most like those in our body.

credit: Samantha Morris, Ph.D./Boston Children's Hospital

credit: Samantha Morris, Ph.D./Boston Children’s Hospital

Some of the biggest potential differences between cells grown in a dish and those in us, is the state of the various genetic switches that turn our genes on and off. Now, a team at Boston Children’s Hospital, the Wyss Institute at Harvard and Boston University has developed a computer algorithm to compare our natural cells to various types of cells grown in the lab.

Many in the field had hoped that the direct conversion of adult cells to other cell types would prove to be the way to go. Unfortunately, the computer program showed that those cells were not nearly as good at mimicking natural cells as cells matured from early stem cells were. However, the team suggests their system points to ways to improve direct conversion. The researchers published two paper on the system they are calling CellNet in the journal Cell August 14 and Genetic Engineering and Biotechnology News did a nice write up of the work.

Willie Nelson advances stem cells for muscular dystrophy.
Really! No, Willie is not in the lab, but he was named an honorary member of the lab and had an endowed chair held by the lab director named for him. He had performed at a concert to raise money to fund the work at UT Southwestern Medical Center in Dallas and the university decided to honor him with the named chair.

In the current paper the lab used the most trendy form of gene modification out there right now, called CRISPR. Researchers are excited about the technology because it can specifically go into our DNA and permanently cut out a mutation. Then our natural genetic machinery can go about making the correct gene. In this case they used it to cut out the error that caused Duchenne muscular dystrophy in a mouse model. After the correction, the mice grew new muscle and got stronger.

The CRISPR technology needs some refinements before it would be ready for use in humans, but the team is working on that along with many others around the country. Their goal: correct the error in patient muscle stem cells so that they can produce a lifetime supply of healthy muscle. The journal Science published their work online August 14 and the HealthCanal website picked up the university press release.

Scientists need to talk to the public. The director of the National Institutes of Health, Francis Collins, visited the University of Washington this week and delivered a message straight from my personal soapbox: Funding for research is in jeopardy and the only way it will be salvaged is for researchers to get more involved in outreach to the public. The Seattle Times quoted him as saying:

“I think it’s at a particularly crucial juncture. If there was a moment to kind of raise consciousness, this is kind of the moment to do that.”

He noted that the chances of a research proposal submitted to NIH getting funded dropped from 40 percent in 1979 to 16 percent now, saying “we’re leaving half the good science on the table.” Part of the solution he suggested was for scientists to get out to Rotary clubs, high school classrooms, and any other public speaking opportunity.

“It seems to me that we all have to spend more of our time, perhaps, as ambassadors for science literacy — trying to explain what we do and why it matters.”

Don Gibbons

Stem Cell Stories that Caught our Eye: “Let it Grow” Goes Viral, Stroke Pilot Study, The Bowels of Human Stem Cells, Tumor ‘Safety Lock.’

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.

“Let it Grow” Goes Viral (and National!): Last week on The Stem Cellar we shared one of our favorite student videos from our annual Creativity Program. The video, a parody of the hit song from the movie Frozen, highlighted the outstanding creativity of a group of high school students from City of Hope in Los Angeles. And now, the song has made a splash nationwide—with coverage from ABC 7 Bay Area and even NBC New York!

Students from the City of Hope practice their routine for the group video

Students from the City of Hope practice their routine for the group video

Watch the full video on our YouTube page.

Stroke Pilot Study Shows Promise. Researchers at Imperial College London are currently testing whether stem cells extracted from a patient’s bone marrow can reverse the after effects of a stroke.

Reporting in this week’s Stem Cells Translational Medicine the team, lead by Dr. Soma Banjeree, describe their pilot study in which they collect a type of bone marrow stem cells called CD34+ cells. These cells can give rise to cells that make up the blood and the blood vessel lining. Earlier research suggested that treating stroke victims with these cells can improve recovery after a stroke—not because they replace the brain cells lost during a stroke, but because they release a chemical that triggers brain cells to grow. So the team decided to take the next step with a pilot study of five individuals.

As reported in a recent news release, this initial pilot study was only designed to test the safety of the procedure. But in a surprising twist, all patients in the study also showed significant improvement over a period of six months post-treatment. Even more astonishing, three of the patients (who had suffered one of the most severe forms of stroke) were living assistance-free. But since the first six months after injury is a time when many patients see improved function, these results need to be tested in a controlled trial where not all patients receive the cells

Immediate next steps include using advancing imaging techniques to more closely monitor what exactly happens in the brain after the patients are treated.

Want to learn more about using stem cells to treat stroke? Check out our Stroke Fact Sheet.

Deep in the Bowels of Stem Cell Behavior. Another research advance from UK scientists—this time at Queen Mary University of London researchers—announces important new insight into the behavior of adult stem cells that reside in the human gastro-intestinal tract (which includes the stomach and intestines). As described in a news release, this study, which examined the stem cells in the bowels of healthy individuals, as well as cells from early-stage tumors, points to key differences in their behaviors. The results, published this week in the journal Cell Reports, point to a potential link between stem cell behavior and the development of some forms of cancer.

By measuring the timing and frequency of mutations as they occur over time in aging stem cells, the research team, led by senior author Dr. Trevor Graham, found a key difference in stem cell behaviors between healthy individuals, and those with tumors.

In the healthy bowel, there is a relative stasis in the number of stem cells at any given time. But in cancer, that delicate balance—called a ‘stem cell niche’—appears to get thrown out of whack. There appears to be an increased number of cells, paired with more intense competition. And while these results are preliminary, they mark the first time this complex stem cell behavior has been studied in humans. According to Graham:

“Unearthing how stem cells behave within the human bowel is a big step forward for stem cell research. We now want to use the methods developed in this study to understand how stem cells behave inside bowel cancer, so we can increase our understanding of how bowel cancer grows. This will hopefully shed more light on how we can prevent bowel cancer—the fourth most common cancer in the UK.”

Finding the ‘Safety Lock’ Against Tumor Growth. It’s one of the greatest risks when transplanting stem cells: the possibility that the transplanted cells will grow out of control and form tumors.

But now, scientists from Keio University School of Medicine in Japan have devised an ingenious method that could negate this risk.

Reporting in the latest issue of Cell Transplantation and summarized in a news release, Dr. Masaya Nakamura and his team describe how they transplanted stem cells into the spinal columns of laboratory mice.

And here’s where they switched things up. During the transplantation itself, all mice were receiving immunosuppressant drugs. But then they halted the immunosuppressants in half the mice post-transplantation.

Withdrawing the drugs post-transplantation, according to the team’s findings, had the interesting effect of eliminating the tumor risk, as compared to the group who remained on the drugs. Confirmed with bioluminescent imaging that tracked the implanted cells in both sets of mice, these findings suggest that it in fact may be possible to finely tweak the body’s immune response after stem-cell transplantation.

Want to learn more about stem cells and tumor risk? Check out this recent video from CIRM Grantee Dr. Paul Knoepfler: Paul Knoepfler Talks About the Tendency of Embryonic Stem Cells to Form Tumors.

Stem cell stories that caught our eye: better cell reprogramming, heart failure and false claims for stem cells

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.

Improving the efficiency of creating stem cell lines.
Ever since researchers first learned to reprogram adult cells to behave like embryonic stem cells in 2007 teams have tried to do it better. The earliest reprogramming resulted in less than one percent of cells converting to the stem cell state. Many years and many reprogramming recipes later some teams have got that up to a few percent, but usually still in the single digits. CIRM-funded researchers at the University of California, San Francisco, have uncovered a path that could yield dramatic increases in efficiency in creating these stem cells. They stepped back to look at what genetic factors were acting as brakes on the reprogramming and have now mapped out multiple brake points that could be inhibited to improve the production of stem cells. HealthCanal ran the university’s press release based on the journal publication in Cell.

Does source of adult cells matter for iPS-type stem cells. When researchers turn adult tissue into embryonic-like iPS cells, they know that the reprogrammed stem cells retain some memory of the type of adult tissue they were, whether it was skin, brain or heart. So, a CIRM-funded team at Stanford set out to do a series of experiments to see if that mattered. They created iPS cells from heart tissue and from skin cells. And initially, there was a difference. The stem cells made from heart more readily matured into heart muscle than those from skin, but over time, as the cells grew in the lab the difference abated. Both types of cells began to function like normal heart muscle. Stanford’s Scope blog wrote about this and a companion paper that were published this week in the Journal of the American College of Cardiology.

Heart progenitor cells, the middlemen between stem cells and adult heart muscle, shown here in green and infected with coxsackie vurus.

Heart progenitor cells, the middlemen between stem cells and adult heart muscle, shown here in green and infected with coxsackie vurus.


Viral heart failure link may be via stem cells
. Our hearts are one of our poorest performing organs when it comes to repairing themselves. The liver does it well. The lining of our guts does it well—the heart not so much. Scientists generally attribute this to the very small number of stem cells we retain in our hearts. If you lose those few, you are in deep trouble. While there are many reasons for heart failure, we have known that a high percent of those who develop this weakening of the heart’s ability to pump blood have signs of having been infected with the coxsackie virus. Researchers at San Diego State University have found out a possible reason why. The virus appears to selectively seek out and destroy the heart stem cells and middlemen progenitor cells. HealthCanal ran the university’s press release based on work published this week in PLOS Pathogens.

Review talks about reality of stem cells in sports.
Over the past year, there has been a parade of headlines about athletes getting their sports injuries treated with stem cells. The EuroStemCell collaborative has published online a great review of the reasons why stem cells might work for some of those conditions, and might not. The piece dutifully starts by noting that none of these treatments have been approved for general use because none have had sufficient testing. Taking muscle, cartilage, tendon and bone repair individually the authors discuss what research has been done and what it shows. In general, the results have not been great, in large part because we haven’t yet figured out what is the best type of cell for each injury and the best way to deliver it.

False claims in stem cell for plastic surgery. CIRM-grantee Michael Longaker at Stanford has called out his fellow plastic surgeons to lead the charge in evaluating the uses of stem cells in cosmetic procedures. In an article in the journal Plastic and Reconstructive Surgery he describes research he did into 50 clinics that showed up in a google search offering stem cell face lifts. While they were claiming to inject age-reversing stem cells, he suggests they were doing no more than the established practice of injecting fat to smooth out wrinkles. While fat does have a few stem cells in it, he could find no evidence that the clinics had the necessary equipment to isolate those cells, and even if they did, there is scant research into whether those stem cells could have any impact. Popular Science and ScienceNewsline both ran stories about the journal article this week.

Don Gibbons

Stem Cell Stories that Caught our Eye: Multiple Sclerosis, Parkinson’s and Reducing the Risk of Causing Tumors

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.

Cell therapy for Parkinson’s advancing to the clinic. A decade-long moratorium on the transplant of fetal nerve tissue into Parkinson’s patient will end in two months when the first patients in a large global trial will receive the cells. BioScience Technology did a detailed overview on the causes for the moratorium and the optimism about the time being right to try again. The publication also talks about what most people in the field believe will be the long-term solution: moving from scarce fetal tissue to nerve cells grown from readily available embryonic stem cells. The author’s jumping off point was a pair of presentations at the International Society for Stem Cell Research in June, which we wrote about at the time. But the BioScience piece provides more background on the mixed results of earlier studies and references to recent journal publications showing long term—as much as 20 year—benefit for some of those patients.

It goes on to describe multiple reasons why, once the benefit is confirmed with fetal cells, moving to stem cells might be the better way to go. Not only are they more readily available, they can be purified in the lab as they are matured into the desired type of early-stage nerve cell. Researchers believe that some of the side effects seen in the early fetal trials stemmed from the transplants containing a second type of cell that caused jerking movements known as dyskinesias. One stem cell trial is expected to start in 2017, which we discussed in June.

Immunity persists through a special set of stem cells. Our immune system involves so many players and so much cell-to-cell interaction that there are significant gaps in our understanding of how it all works. One of those is how we can have long-term immunity to certain pathogens. The T-cells responsible for destroying invading bugs remember encountering specific ones, but they only live for a few years, generally estimated at five to 15. The blood-forming stem cells that are capable of generating all our immune cells would not have memory of specific invaders so could not be responsible for the long term immunity.

Now, an international team from Germany and from the Hutchison Center in Washington has isolated a subset of so-called “memory T-cells” that have stem cell properties. They can renew themselves and they can generate diverse offspring cells. Researchers have assumed cells like this must exist, but could not confirm it until they had some of the latest gee-wiz technologies that allow us to study single cells over time. ScienceDaily carried a story derived from a press release from the university in Munich and it discusses the long-term potential benefits from this finding, most notably for immune therapies in cancer. The team published their work in the journal Immunity.

Method may reduce the risk of stem cells causing tumors. When teams think about transplanting cells derived from pluripotent stem cells, either embryonic or iPS cells, they have to be concerned about causing tumors. While they will have tried to mature all the cells into a specific desired adult tissue, there may be a few pluripotent stem cells still in the mix that can cause tumors. A team at the Mayo Clinic seems to have developed a way to prevent any remaining stem cells in transplants derived from iPS cells from forming tumors. They treated the cells with a drug that blocks an enzyme needed for the stem cells to proliferate. Bio-Medicine ran a press release from the journal that published the finding, Stem Cells and Development. Unfortunately, that release lacks sufficient detail to know exactly what they did and its full impact. But it is nice to know that someone is developing some options of ways to begin to address this potential roadblock.

Multiple sclerosis just got easier to study. While we often talk about the power of iPS type stem cells to model disease, we probably devote too few electrons to the fact that the process is not easy and often takes a very long time. Taking a skin sample from a patient, reprogramming it to be an iPS cell, and then maturing those into the adult tissue that can mimic the disease in a dish takes months. It varies a bit depending on the type of adult tissue you want, but the nerve tissue that can mimic multiple sclerosis (MS) takes more than six months to create. So a team at the New York Stem Cell Foundation has been working on ways to speed up that process for MS. They now report that they have cut the time in half. This should make it much easier for more teams to jump into the effort of looking for cures for the disease. ScienceCodex ran the foundations press release.

Stem cell stories that caught our eye: need for mature fat, Down syndrome, autism and those sweet pup faces

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.

Embryonic stem cells and that sweet puppy face. Could altered stem cells give our pups those floppy ears and adorable faces? Research from Humboldt University in Berlin suggests that is the case. They speculate that when people began to domesticate wild animals they were unwittingly breeding for smaller adrenal glands that are responsible for the “fight-or-flight” syndrome. But those glands arise from a group of stem cells in the developing embryo, the neural crest, that is also responsible for many other aspects of the animal including parts of the skull and the ears.

Annika, a member of the author's "pack," shows the floppy ears and narrow face of domestication. The seat on the furniture could be another clue.

Annika, a member of the author’s “pack,” shows the floppy ears and narrow face of domestication. The seat on the furniture could be another clue.

Researchers have noted since Darwin’s time that these signs of “domestication syndrome” with its floppy ears and narrow faces carry across a broad range of domestic animals. The German team said that the genetic alterations of neural crest stem cells could explain this “hodge-podge of traits.”

The research was published in the journal Genetics and got wide pick up with a fun piece on Mashable and a bit more detail about the science in Pacific Standard Magazine.

Stress might make fat go rogue. It is not something dieters will want to hear, but in order to stay healthy your fat stem cells need to mature into adult fat tissue. When they don’t fat can accumulate at high levels in the bloodstream and within existing cells. A team at Boston University suggests that stress plays a role in how the body processes fat by inhibiting the maturation of fat stem cells. They identified two proteins that act as relay switches to regulate the fat stem cells. That signaling pathway now becomes a target for discovering drugs that might improve our handling of fat, even in times of stress. The team published their work in the Journal of Biological Chemistry and HealthCanal picked up the university’s press release.

Support cells linked to Down syndrome. CIRM-funded researchers at the University of California, Davis have found that the errors in nerve development in Down syndrome may be caused by abnormal functioning of the cells that are supposed to support them, the glial cells. The team started by reprogramming skin cell samples from people with Down syndrome into iPS type stem cells. They then matured those cells in two batches, one into neurons and one into glial cells. The nerves did not seem different from normal nerves but the glial cells produced an abnormally high level of a particular protein. When they mixed the two cell types together, that protein appeared to kill off part of the nerves.

What is intriguing, when they treated the mixed cells with a simple antibiotic the nerve damage did not occur. If the protein only has its negative impact on the developing brain, the finding opens up the possibility of preventive treatment for women who find their fetus has the third chromosome distinctive of Down syndrome. The researchers published their findings in Nature Communication and Science Daily ran a story on the work.

Pros and cons of the large autism trial. Using stem cells to try to treat autism provokes a lot of raw emotion in our field. I frequently field questions from desperate mothers wanting to know where they can take the umbilical cord stem cells they have stored in a freezer to treat their child with autism. I tell them about some of the controversies about this treatment and the need for more data before we know how to use the cells right, if there is any chance they can help at all. The Simons Foundation Autism Research Initiative published a well-balanced analysis of the first large clinical trial trying to answer those questions.

The piece has a skeptic rightfully noting that the type of stem cells in cord blood cannot make replacement cells for the poorly functioning nerve cells in people with autism. It also discusses the possibility that those stem cells might stimulate the person’s own cells to make some of the needed repairs. The trial, which will randomly assign patients to stem cell therapy or no therapy, is being led by Duke University’s Joanne Kurtzenburg, who is described by one outside expert as “the right person to do this.” She is a well-known leader in the field and I would love to have some data to share with parents.

CIRM hosted a group of international experts in autism to look at ways stem cells could foster therapies in autism that produced this report. One of the main suggestions was to use iPS type stem cells to model the disease as shown in this video.

Don Gibbons

Stem Cell Stories that Caught our Eye: Gene Rx, New and Rejuvenated Blood Stem Cells and Budget Cuts

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.

Tinkering with stem cell genes safe. Research at the Salk Institute provides some reassurance that using gene-editing techniques to correct disease-causing mutations in stem cells is safe. This type of intervention aims to give people a corrected version of a gene that can produce a functional protein to replace the bad one they were born with, such as the hemoglobin gene in sickle cell disease. The CIRM-funded Salk team made gene corrections with both of the two most common gene-editing techniques: using a virus to carry the correct gene into the cell, and using an enzyme to cut and splice the genes. The fear, the lead researcher said in Space Daily, has been that this gene manipulation would cause unwanted mutations. Instead the team found that the very small number of mutations in the edited cells did not exceed the number in normal cells growing in the lab for the same length of time.

Blood cells

This is great news for CIRM, since eight of our Disease Teams—all of which have the goal of moving therapies into the clinic—use gene modification techniques. These include efforts to correct the genetic mutation that causes sickle cell disease and beta thalassemia.

Interview with Nobelist on stem cell potential. The Raw Story ran an interview with Nobel Laureate Martin Evans about the field he helped to create when he first isolated mouse embryonic stem cells in 1981. He won the Nobel in 2007 for later work in which he used embryonic stem cells to create specific gene modifications in mice. He said we are “just scraping the surface” in unlocking the potential of stem cells to change medicine. He also addresses various aspects of reprogramming cells to become different types of tissue and provides a bit of advice to young scientists: “You should not believe in all that you read.”

Keep your blood stem cells acting young. Blood stem cells, like most of the adult stem cells in our various tissues, become less adept at doing their job of replenishing our tissues as we age. A team at New York’s Mount Sinai has fingered the decrease of a specific protein in older stem cells as the culprit. That protein, SIRT1, was not a surprise as it has been implicated in other aging research. When laboratory animals eat a severely calorie restricted diet and live longer, SIRT1 is active at a higher than normal level. So, it makes some sense that low levels of SIRT1 would be associated with conditions of aging. The team now wants to see if increasing SIRT1 levels can put the kick of youth back into older blood stem cells. The web portal Hospital Newspaper ran a story on the research that the team published in Stem Cell Reports.

Or use a new way to create blood cells. If you can’t get your own blood stem cells to behave like vigorous youthful cells another option is to get some new one. The problem is many folks cannot find a matching donor and previous attempts to grow them from earlier stage stem cells have not worked. Using either embryonic or reprogrammed iPS type stem cells to try to grow large quantities of blood-forming stem cells has always resulted in immature cells that cannot make all the blood cells and don’t readily take up residence—engraft—in the patient. Researchers at Cornell Medical College may have solved this problem by growing the stem cells in a more natural environment. They grew them in a bed of cells like those that would have surrounded them in blood vessels in a developing fetus. The resulting cells engrafted in mice and produced nearly all the components of blood. They had a few lingering problems with creating the immune system’s T cells, but got much closer than previous work. Device Space picked up the medical school’s press release.

This goal of creating fully functional blood stem cells is sufficiently important but vexing to the research community that CIRM organized an international workshop on the topic. You can read the resulting whitepaper “Breaking the Bottleneck.”

Donors needed to power discovery. With federal support for research shrinking many institutions are relying more and more on donors to fund the research that leads to discoveries and eventually therapies. The New York based web publication Capital Playbook painted a picture of the deficit citing a 22 percent reduction in the inflation-adjusted budget for the National Institutes of Health since 2003. It goes on to quote senior scientists fearing the loss of a generation of scientists. A great comment came from my friend and former colleague David Scadden, co-director of the Harvard Stem Cell Institute. “They are seeing their senior mentors spending more and more time writing grants and going hat in hand. That’s not a good way to inspire the best and brightest.”

Don Gibbons