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

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

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

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

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

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

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

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

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

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

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

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

Stem cell stories that caught our eye: brain repair, bone repair and boosting old 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.

Potential drugs to make brain stem cells do a better job.
Patients with strokes and neurodegenerative diseases usually have a double whammy of faulty self-repair mechanisms. The brain is one of those organs that has few adult stem cells and most patients are decidedly senior citizens with older stem cells that are less robust.

Most teams looking to get around that problem implant stem cells from young donors, but that can be invasive and the cells often don’t survive long in a non-native environment. So, several groups are looking for ways to get those few stem cells in our adult brain to do a better job. One team, at the Australian company Novogen, announced this week that they had discovered a class of compounds that seems to promote the growth and activation of adult brain stem cells.

Yahoo Finance picked up the company’s press release, which is a little excessively promotional, but does get the basic facts straight. If these compounds end up working in people, they could make a big difference in healing neural conditions.

Another option for boosting older stem cells. A team at Moscow State University has published a review of the research into why stem cells in older people are not as good at repairing damage, and some early attempts to boost the performance of those cells. The short write up of the paper in Genetic Engineering & Biotechnology News gives very little detail, but it does have a link to the full article in BioResearch Open Access, which is relatively understandable.
old mouse
They give some focus to the use of a patient’s mesenchymal stem cells from their bone marrow or fat to treat heart problems. They site a few studies that suggest if you stress the cells in the lab after you harvest them from the patient and before you inject the back to where they are needed, they seem to do a better job. In particular, they cited growing the cells in an extremely low-oxygen environment.

A new type of bone stem cell discovered.
The dogma has been that mesenchymal stem cells (MSCs) found in the bone give rise to any new bone or cartilage we may need as adults. But those cells also have roles making a few other types of cells. Now, researchers on both coasts, at Stanford and Columbia, have discovered a more specific stem cell that just gives rise to bone and cartilage.

Both research papers appeared in today’s online edition of the journal Cell and Genetic Engineering & Biotechnology News wrote up the Columbia study. It points out that while it remains true that MSCs can generate bone, the newly discovered cells may be more efficient doing it and may be better targets for therapies that try to speed bone healing. The university’s press release was picked up by ScienceDaily and provides a bit more detail.

The Stanford team, after isolating the bone-specific stem cells, took the work another step. That work could be key to helping older patients who often have slow healing fractures because they have fewer active stem cells of any type. The CIRM-funded researchers discovered a set of genetic factors that can be used to reprogram fat cells to become the specialized bone stem cell. In a press release picked up by HealthCanal one of the senior authors on the paper, Michael Longaker, described how the finding might allow patients to avoid the painful procedure of harvesting bone for bone grafts.

“Using this research you might be able to put some of your own fat into a biomimetic scaffold, let it grow into the bone you want in a muscle or fat pocket, and then move that new bone to where it’s needed.”


The cancer stem cell debate explained.
Jocelyn Kaiser wrote the best, most balanced, piece I have read on the whole debate over whether cancer stem cells exist, and more important, will targeting them really make a difference in the number of patients we cure of cancer? Even though it appears in the journal Science it is written as a feature and is pretty approachable to a lay audience.

A book for stem cell wonks.
David Warburton, a CIRM-grantee at Children’s Hospital Los Angeles, has published a book of essays that cover a broad swath of the field of regenerative medicine. The essays range from the minutia of what it takes to set up a stem cell lab to the pipeline of potential therapies. I have to admit I have a personal prejudice to like the book given his quote in the press release on EurekAlert:

“Those of us working in this field in California are positively impacted by the critical funding provided by the citizens of the state through the California Institute for Regenerative Medicine. I believe this book shows that the hope behind CIRM – the hope that stem cells can really revolutionize medicine and human health – is fully justified.”

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

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Here are some stem cell stories that caught our eye this past week. Some are groundbreaking science, others are of personal interest to us, and still others are just fun.

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

Brown fat derived from stem cells. Image courtesy of Harvard

Brown fat derived from stem cells. Image courtesy of Harvard

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

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

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

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

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

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

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

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

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

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

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

Stem cell stories that caught our eye: organ replacement, ovarian cancer and repairing damaged 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.

Numbers on organ shortage and review of lab replacements.
Vox, the four-month-old web site, is rapidly becoming a credible news source with more than five million page views so far. With a reputation for explaining the facts behind the news, it was nice to see they tackled the organ shortage and how researchers are using stem cells to try to solve it.

organ shortage.0After providing data on the incredible need, the author addressed several key advances, as well as remaining hurdles, to using stem cells to build replacement organs in the lab. She notes that an important step to growing an organ is being able to grow all the various types of cells that make up a complex organ.

“Each specialized type of cell in your body needs certain chemical clues from its environment in order to thrive and multiply. And even a simple-seeming body part, like a urethra, requires more than one cell type, arranged in certain ways relative to one another.”

In addition to a chart with data on organ donation and need, the article provides a link to a fun video on growing a rat lung in the lab. The author closes with the fact that the greatest need is for kidneys and a discussion of how tough they are to make because of the complex mix of tissues needed.

An advance in building kidneys also made the journals this week, with a press release from Cellular Dynamics describing how their lab grown cells succeeded in coating the inside of blood vessels in a scaffold for a rodent kidney.

Stem cell factors heal damaged hearts. The American Heart Association met in Chicago this week and as always the week of their fall enclave generates several news stories. Genetic Engineering & Biotechnology News wrote up a study from the Icahn School of Medicine at Mount Sinai in New York that suggested how your own stem cells might be recruited to repair damage after a heart attack.

The New York team used a form of gene therapy that introduced the genes for “stem cell factors” that they believe could summon a type of stem cell that some have suggested can repair heart muscle. Although, whether those cells, called c-Kit positive heart stem cells, are actually the cause of the repair remains a subject of debate. They did show that their treatment improved heart function and decreased heart muscle death in the rodent model they were using.

Stem cells improve survival of skin grafts.
With so many soldiers returning from deployments needing reconstructive surgery, several teams at our armed services medical institutes are trying to solve the problem of the soldiers’ immune systems rejecting large skin grafts from donors. One team reported a potentially major advance in the Journal Stem Cells Translational Medicine and the web site benzinga picked up the journal’s press release.

Working in mice the team got the best skin graft survival in animals that received two types of stem cells to induce immune tolerance to the graft. The mice received fat-derived stem cells from humans and an infusion of a small number of their own bone marrow stem cells. The grafts showed no sign of rejection after 200 days, a very long time in a mouse’s life. In the press release, the editor of the journal, Anthony Atala, suggested the results could have broad implications for the field.

“The implications of this research are broad. If these findings are duplicated in additional models and in human trials, there is potential to apply this strategy to many areas of transplantation.”

Leukemia drug may also work in ovarian cancer. The antibody named for CIRM in recognition of our funding of its discovery, cirmtuzumab, which is already in clinical trials in humans for leukemia, may also be effective in one of the most stubborn tumors, ovarian cancer.

Ovarian cancer cells

Ovarian cancer cells

The University of California, San Diego, team led by Thomas Kipps published a study in the Proceedings of the National Academy of Sciences this week showing that in mice the antibody kept transplanted human ovarian cancer cells in check. The tumor that is characterized by rapid spread did not metastasize at all. HealthCanal picked up the university’s press release explaining how the new drug works. You can read about the CIRM-funded clinical trial in leukemia in our fact sheet.

Versatile fingernail stem cells.
The stem cells that regrow our nails are prodigious little critters forcing us to constantly cut or file. But it turns out they are also versatile. They can stimulate nail growth but also growth of skin around the nail.

But if our nails get injured they become single minded and only make nail cells. A team at the University of Southern California has discovered that at the time of injury a particular protein signal gets turned on directing the stem cells to focus on the nails. So, the team is now looking for other signaling proteins that might direct these versatile cells to make other tissues making them potential tools for healing amputations. ScienceDaily picked up the university’s press release.

Don Gibbons

Stem cell stories that caught our eye: gene editing tools, lung repair in COPD and big brains

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.

Correcting the genetic error in sickle-cell disease might be as simple as editing the text.

Correcting the genetic error in sickle-cell disease might be as simple as editing the text [Credit: Nature News].

Review of the many ways to edit defective genes. Nature’s news section did a nice review of the many ways blood-forming stem cells can be genetically altered to correct diseases caused by a single mutation. If you have been following the recently booming field of gene therapy, you may have a hard time keeping all the items in the gene editing toolbox straight. The Nature author provides a rundown on the leading contenders—viral vectors, zinc fingers, TALENs and CRISPRs. Early in the piece she describes why researchers are so excited by the field.

“Although most existing treatments for genetic diseases typically only target symptoms, genetic manipulation or ‘gene therapy’ goes after the cause itself.”

Much of the article talks about work by CIRM grantees. It describes work by Don Kohn at the University of California, Los Angeles, on vectors and zinc fingers, as well as work by Juan Carlos Izpisua Belmonte at the Salk Institute using TALENS and CRISPRs. We explain Kohn’s work treating sickle cell disease in our Fact Sheet.

Getting lungs to repair themselves. A research team at Jackson Labs in Maine has isolated a stem cell in lungs that appears to be able to repair damage left behind by severe infections. They hope to learn enough about how those stem cells work to enlist them to repair damage in diseases like Chronic Obstructive Pulmonary Disease (COPD).

They published the work in Nature and ScienceDaily picked up the lab’s press release. It quotes the lead researcher, Wa Xian on the hope they see down the road for the 12 million people in the U.S. with COPD:

“These patients have few therapeutic options today. We hope that our research could lead to new ways to help them.”

Making middle-man cells more valuable. The University of Wisconsin lab of Jamie Thomson, where human embryonic stem cells (ESCs) were first isolated, has found a way to make some of the offspring of those stem cells more valuable.

We have often written that for therapy, the desired cell to start with is not an ESC or even the end desired adult tissue, but rather a middleman cell called a progenitor. But those cells often don’t renew, or replicate themselves, very well in the lab. Ideally researchers would like to have a steady supply of progenitor cells that could be pushed to mature further only when needed. The Thomson lab found that by manipulating a few genes they could arrest the development of progenitors so they constantly renew themselves. ScienceNewsline picked up the press release from the University’s Morgridge Institute that houses the Thomson lab.

Link found to human’s big brains. A CIRM-funded team at the University of California, San Francisco, isolated a protein that seems to be responsible for fostering the large brain size in humans compared with other animals. Human brain stem cells need the protein, dubbed PDGFD, to reproduce.

The team found that the protein acts on parts of the brain that have changed during mammalian evolution. It is not active at all in mice brains, for example. So, if someone accuses you of being a smart aleck just tell them you can’t help it, it’s your PDGFD. HealthCanal ran the university’s press release, which provides a lot more detail of how the protein actually helps give us big heads.

Don Gibbons

Stem cell stories that caught our eye: heart repair, epilepsy and comparing cloned and reprogrammed 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.

Reminding broken hearts how to mend them selves.
After years of tracking down the right genetic buttons a team at the Salk Institute in La Jolla has taught a mammal to do what zebra fish do naturally, repair a severely damaged heart. While all our cells have the genetic code for building whole organs those genes seem to be switched off in all higher animals, but active in some more primitive species like zebra fish and salamanders.

New cells (red) repairing injury in a zebra fish heart.

New cells (red) repairing injury in a zebra fish heart.

Starting a decade ago the researchers measured the gene activity during heart repair in the fish. They found many genes that had their on-off status change during repair. They then looked to see which of those genes had been preserved during evolution to mammal species. They found four genes that were turned off during repair in the fish but were turned on in the mice they were using.

When, with CIRM funding, they inserted genetic signals to turn off those genes in the mice, they saw significant repair of the damaged heart. There are many steps between this advance and getting human hearts to repair them selves—notably finding a way to introduce the genetic signals without using the virus used in this study. HealthCanal picked up the institute’s press release.

Cloned stem cells pretty much like reprogrammed stem cells. In the early days of stem cell research there was a great deal of excitement about the possibility of creating stem cells that genetically match a patient by a process commonly called cloning. This process of taking the genetic storehouse of a cell, the nucleus, and inserting it into a donor egg had been relatively easy in mice. But it turned out quite difficult in humans and was only accomplished last year.

During the years of failed attempts at this process known as nuclear transfer in humans an alternative came into the field. The Nobel prize-winning discovery that you can reprogram any adult cell to act like an embryonic stem cell gave us a new way to create personalized stem cells that genetically match a patient. But ever since that 2008 advance, the research community has fretted over whether those new stem cells called iPS cells really match embryonic stem cells. The iPS cells came from older cells that had lived through many opportunities for mutation and the genetic factors used to reprogram them added further opportunities for mutation.

Researchers at the New York Stem Cell Foundation’s in house lab have now compared the two types of cells with several layers of genetic analysis. They found the same level of mutation in the iPS cells and the cells from nuclear transfer lending some reassurance to the use of iPS cells going forward. HealthCanal ran the foundation’s press release.

A more efficient way to make cloned stem cells. Even though a team in Oregon overcame the obstacles to creating stem cells by nuclear transfer last year, and the feat has been repeated by the New York team above and others, it remains terribly inefficient. So, several groups are working on better ways to make these potentially valuable cells.

A former colleague now at Children’s Hospital, Boston wrote a nice explanation of how researchers are going about making these cloned cells easier in the hospital’s blog, Vector.

Stem cells reduced seizures.
The seizures endured by people with many forms of epilepsy originate from genetic defects in their nerves. So, a team at McClean Hospital outside of Boston implanted healthy nerves grown from embryonic stem cells in mice with genetically linked seizures. Half the mice no longer had seizures and the other half had their seizure frequency reduced.

The type of nerves transplanted are called interneurons, which are known to be the nerves that reduce firing of signals. In epilepsy nerve signals are hyperactive. The team is now working on methods to mature the stem cells into purer populations of just the desired interneurons. ClinicalSpace picked up the hospital’s press release.

Don Gibbons

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.