Stem Cell Stories that Caught our Eye: Skin Cells to Brain Cells in One Fell Swoop, #WeAreResearch Goes Viral, and Genes Helps Stem Cells Fight Disease

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.

Building a Better Brain Cell. Thanks to advances in stem cell biology, scientists have found ways to turn adult cells, such as skin cells, back into cells that closely resemble embryonic stem cells. They can then coax them into becoming virtually any cell in the body.

But scientists have more recently begun to devise ways to change cells from one type into another without first having to go back to a stem cell-like state. And now, a team from Washington University in St. Louis has done exactly that.

As reported this week in New Scientist, researcher Andrew Yoo and his team used microRNAs—a type of ‘signaling molecule’—to reprogram adult human skin cells into medium spiny neurons(MSNs), the type of brain cell involved in the deadly neurodegenerative condition, Huntington’s disease.

“Within four weeks the skin cells had changed into MSNs. When put into the brains of mice, the cells survived for at least six months and made connections with the native tissue,” explained New Scientist’s Clare Wilson.

This process, called ‘transdifferentiation,’ has the potential to serve as a faster, potentially safer alternative to creating stem cells.

#WeAreResearch Puts a Face on Science. The latest research breakthroughs often focus on the science itself, and deservedly so. But exactly who performed that research, the close-knit team who spent many hours at the lab bench and together worked to solve a key scientific problem, can sometimes get lost in the shuffle.

#WeAreResearch submission from The Thomson Lab at the University of California, San Francisco. This lab uses optogenetics, and RNAseq to probe cell fate decisions.

#WeAreResearch submission from The Thomson Lab at the University of California, San Francisco. This lab uses optogenetics, and RNAseq to probe cell fate decisions.

Enter #WeAreResearch, a new campaign led by the American Society for Cell Biology (ASCB) that seeks to show off science’s more ‘human side.’

Many California-based stem cell teams have participated—including CIRM grantee Larry Goldstein and his lab!

Check out the entire collection of submissions and, if you’re a member of a lab, submit your own. Prizes await the best submissions—so now’s your chance to get creative.

New Genes Help Stem Cells Fight Infection. Finally, UCLA scientists have discovered how stem cells ‘team up’ with a newly discovered set of genes in order to stave off infection.

Reporting in the latest issue of the journal Current Biology, and summarized in a UCLA news release, Julian Martinez-Agosto and his team describe how two genes—adorably named Yorkie and Scalloped—set in motion a series of events, a molecular Rube Goldberg device, that transforms stem cells into a type of immune system cell.

Importantly, the team found that without these genes, the wrong kind of cell gets made—meaning that these genes play a central role in the body’s healthy immune response.

Mapping out the complex signaling patterns that exist between genes and cells is crucial as researchers try and find ways to, in this case, improve the body’s immune response by manipulating them.

Stem Cell Stories that Caught our Eye: Perspective on “Walking” Patient, Blood Stem Cells have a Helper and Three Clinical Trials at One Campus

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.

Some perspective on nasal stem cells and ”walking” patient. PZ Meyers writing on ScienceBlogs did a good job of putting some perspective into the hype in many news outlets about the spinal cord injury patient who was treated with nasal stem cells. He starts out admitting he was “incredulous” that there was anything to the study, but after a thorough reading of the actual journal article he was convinced that there was some real, though modest gain in function for the patient. His conclusion:

“Sad to say, the improvements in the man’s motor and sensory ability are more limited and more realistic than most of the accounts would have you think.”

The research team actually reported on three patients. One got barely noticeable improvement; the patient in the news reports regained about 25 percent of function—which is indisputably a major gain in this population—and the third was somewhere in between.

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Meyer speculated about a reason for the improvements that was left out of most press reports. In addition to the stem cell harvested from the patients’ own nasal passages injected on either side of the injury the team also harvested nerve fibers from the patients legs and transplanted them across the site of the injury. They hoped the nerve strands would act as a bridge for the stem cells to grow and close the gap. It is also possible that being nerve cells they could provide the right cell-to-cell signals directing the nasal stem cells to become nerves. Meyers closed with an appropriate summary:

“I think there’s good reason to be optimistic and see some hope for an effective treatment for serious spinal cord injuries, but right now it has to be a realistic hope — progress has been made. A cure does not exist.”

Body’s own helper for blood stem cells found. In a case of the children ordering around the parents, a team at the Stowers Institute in Kansas City found that one of the progeny of blood-forming stem cells in the bone marrow can control the activity of the stem cells. In particular, they were looking at megacarocytes, the relatively rare bone marrow cells that normally produce the blood platelets you need for clotting a wound.

Blood stem cells are the most common stem cell therapy today, but one plagued by our limited ability to control their growth. Knowing this involvement of their offspring gives researcher a new avenue to search for ways to grow the much needed parent stem cells. Genetic Engineering & Biotechnology News wrote up the findings.

(Yes, I may be the only person in World Series-obsessed San Francisco writing something positive about Kansas City this week.)

Three clinical trails launched at just one campus. We have written individually about three clinical trials that began in the last month at the University of California, San Diego. Now, the university has written a good wrap up of the three trials that got posted to ScienceDaily.

Collectively, the three trials show the breadth of stem cell research starting to reach patients. One trial, for diabetes, uses cells derived from embryonic stem cells encased in a pouch to protect them from immune rejection. Another uses cells derived from fetal nerve stem cells to treat spinal cord injury. And the third involves a drug that targets the cancer stem cells that are believed to cause much of the spread of the disease and resistance to chemotherapy in cancer patients.

CIRM is funding two of the three trials and supported much of the basic science that led to the third. We expect to be funding 10 projects with approved clinical trials by the end of the year. The field is moving.

Don Gibbons

Stem cell stories that caught our eye: Some good news got a little overplayed on blindness and Alzheimer’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.

Stories on blindness show too much wide-eyed wonder. While our field got some very good news this week when Advanced Cell Technologies (ACT) published data on its first 18 patients treated for two blinding diseases, many of the news stories were a little too positive. The San Diego Union Tribune ran the story from Associated Press writer Maria Cheng who produced an appropriately measured piece. She led with the main point of this early-phase study—the cells implanted seem to be safe—and discussed “improved vision” in half the patients. She did not imply their sight came back to normal. Her third paragraph had a quote from a leading voice in the field Chris Mason of University College London:

“It’s a wonderful first step but it doesn’t prove that (stem cells) work.”

The ACT team implanted a type of cell called RPE cells made from embryonic stem cells. Those cells are damaged in the two forms of blindness tested in this trial, Stargardt’s macular dystrophy and age-related macular degeneration, the leading cause of blindness in the elderly. Some of the patients have been followed for three years after the cell transplants, which provides the best evidence to date that cells derived from embryonic stem cells can be safe. And some of the patients regained useful levels of vision, which with this small study you still have to consider other possible reasons for the improvement, but it is certainly a positive sign.

CIRM funds a team using a different approach to replacing the RPE cells in these patients and they expect to begin a clinical trial late this year

Stem cells create stronger bone with nanoparticles.   Getting a person’s own stem cells to repair bad breaks in their bones certainly seems more humane than hacking out a piece of healthy bone from some place else on their body and moving it to the damaged area. But our own stem cells often can’t mend anything more than minor breaks. So, a team from Keele University and the University of Nottingham in the U.K. laced magnetic nanoparticles with growth factors that stimulate stem cell growth and used external magnets to hold the particles at the site of injury after they were injected.

It worked nicely in laboratory models as reported in the journal Stem Cells Translational Medicine, and reported on the web site benzinga. Now comes the hard step of proving it is safe to test in humans

Stem cells might end chronic shortage of blood platelets. Blood platelets—a staple of cancer therapy because they get depleted by chemotherapy and radiation—too often are in short supply. They can only set on the shelf for five days after a donation. If we could generate them from stem cells, they could be made on demand, but you’d have to make many different versions to match various peoples’ blood type. The latter has been a bit of a moot point since no one has been able to make clinical grade platelets from stem cells.

plateletsA paper published today by Advanced Cell Technologies may have solved the platelet production hurdle and the immune matching all at once. (ACT is having a good week.) They produced platelets in large quantities from reprogrammed iPS type stem cells without using any of the ingredients that make many iPS cells unusable for human therapy. And before they made the platelets, they deleted the gene in the stem cells responsible for the bulk of immune rejection. So, they may have created a so-called “universal” donor.

They published their method in Stem Cell Reports and Reuters picked up their press release. Let’s see if the claims hold up.

Alzheimer’s in a dish—for the second time. My old colleagues at Harvard got a little more credit than they deserved this week. Numerous outlets, including the Boston Globe, picked up a piece by The New York Times’ Gina Kolata crediting them with creating a model of Alzheimer’s in a lab dish for the first time. This was actually done by CIRM-grantee Lawrence Goldstein at the University of California, San Diego, a couple years ago.

But there were some significant differences in what the teams did do. Goldstein’s lab created iPS type stem cells from skin samples of patients who had a genetic form of the disease. They matured those into nerve cells and did see increased secretion of the two proteins, tau and amyloid-beta, found in the nerves of Alzheimer’s patients. But they did not see those proteins turn into the plaques and tangles thought to wreak havoc in the disease. The Harvard team did, which they attributed, in part, to growing the cells in a 3-dimensional gel that let the nerves grow more like they would normally.

The Harvard team, however, started with embryonic stem cells, matured them into nerves, and then artificially introduced the Alzheimer’s-associated gene. They have already begun using the model system to screen existing drugs for candidates that might be able to clear or prevent the plaques and tangles. But they introduced the gene in such a way the nerve cells over express the disease gene, so it is not certain the model will accurately predict successful therapies in patients.

Don Gibbons

Stem cell stories that caught our eye: heart disease, blindness and replacement teeth

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.

Review looks at approaches to blindness.
The Scientist published a nice lay level overview of various teams’ work to use stem cells to cure blindness. The bulk of the story covers age-related macular degeneration, the most common form of blindness in the elderly, with six approaches discussed and compared including the CIRM-funded California Project to Cure Blindness.

Dennis Clegg, one member of the California project team, was featured in a story posted by his university

The piece smartly includes an overview of the reasons eye diseases make up a disproportionate number of early stem cell trials using stem cells from sources other than bone marrow. Many in the field view it as the perfect target for early therapies where safety will be a main concern. It is a confined space so the cells are less likely to roam; it is small so fewer cells will be needed; and it has reduced immune activity so less likely to reject new cells.

The author describes three approaches to using cells derived from embryonic stem cells, one using iPS-type stem cells, one using fetal-derived nerve stem cells and one using cells from umbilical cord blood. An ophthalmologist from the University of Wisconsin who was not associated with any of the trials offered a fair assessment:

“We’re pushing the boundaries of this technology. And as such, we expect there to be probably more bumps in the road than smooth parts.”


A heart of gold, nanoparticles that is.
Most teams using scaffolds seeded with cells to create patches to strengthen damaged hearts start with animal material to create the scaffold, which can cause immune problems. An Israeli group has developed a way to use a patient’s own fat tissue to create these scaffolds. But that left the remaining problem of getting cells in a scaffold to beat in unison with the native heart. They found that by lacing the scaffold with gold nanoparticles they could create an effective conduction system for the heart’s electrical signals.

A story in ScienceDaily quotes the lead researcher Tal Dvir:

“The result was that the nonimmunogenic hybrid patch contracted nicely due to the nanoparticles, transferring electrical signals much faster and more efficiently than non-modified scaffolds.”

If you read the story parts of it are a little overwrought. The headline, “A Heartbeat away? Hybrid patch could replace transplants,” pushes credibility on two fronts. The first half suggests this therapy is imminent, rather than the reality of years away. Patches could only replace the need for transplants. They could never work as well as a full new heart, but since we only need partial function in our heart to live relatively OK, and they might be safer than a transplant they might replace the need.

Could teeth be first complex organ stem cell success? The Seattle Times did a pretty thorough story about why the tooth might be the first complex organ replaced via stem cells and regenerative medicine. While it is a complex organ with multiple layers, a blood system and a nervous system, it does not have moveable parts and we understand each part better than with other major organs.

The paper starts with a good reminder of just how far dental hygiene has come, with few elderly people needing dentures today—leaving the need for new teeth, suggests the author, to people such as hockey players.

A CIRM-funded team is investigating various ways to build a new tooth.

Even the Tea Party would like this regulation.
We have roughly as many genes as a frog, but are much more complicated. Our higher function evolved in part by making our genes more highly regulated. A CIRM-funded team now reports that this particularly applies to our “jumping genes,” and no that does not have anything to do with jumping frogs.

The work focuses on transposons, bits of our DNA that literally move around, or jump, between our functional genes and change how they are turned on or off. We also have evolved a set of genes to control the jumping genes, and the researchers at the University of California, Santa Cruz, suggest that evolution has been a never ending tug of war between the jumping genes and the genes that are supposed to control them.

HealthCanal ran the university’s press release, which quotes lead researcher Sofie Salama:

“We have basically the same 20,000 protein-coding genes as a frog, yet our genome is much more complicated, with more layers of gene regulation. This study helps explain how that came about.”

Don Gibbons

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.