Stem cell stories that caught our eye; viral genes in embryos, underuse of transplants and joint pain clinics

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.

Ancient viral invaders help make us, us. The cells of our ancestors millions of years ago may have found a way to turn viral invasion into a good thing. This genetic lemons-to-lemonade tale comes from a team in Singapore that meticulously looked at 650,000 bits of virus genes that have been left behind in our cells after viral infections.

Retroviruses like HIV can only replicate by integrating their genes into ours and getting our cellular machinery to make new copies of themselves. Biologists have long known that they often leave behind bits of their genes, but had assumed this became part of the “junk DNA” that does not serve any function and that makes up the bulk of the genetic material in our cells. That scenario has started to change over the past few years as teams have reported examples of those retroviral genetic elements playing a role in the regulation—the turning on and off—of our functional genes.
virus
Jonathan Goke, the lead researcher on the project at the Genome Institute of Singapore, wrote that roughly 1,400 of those viral gene elements were involved in the very early stages of embryo development, helping determine how cells decide to mature into different types of tissue. They seem to be needed for determining who we are.

In an article on the website science 2.0 Goke speculated that these viruses may have been able to speed-up evolution by making changes in gene function faster than random mutation.

Blood stem cell transplants under used. Even as the number of blood stem cell transplants ever performed has passed the one million mark, a new report warns that lives are at risk because too many patients that could benefit are not getting these transplants. Blood stem cell transplants, which started as bone marrow transplants, provide the only shot at life-saving therapy for many patients, mostly those with blood cancers.

An international team, led by Dietger Niederwieser of the University Hospital Leipzig in Germany, found a dramatic under use of donor cells for transplants that varied widely around the world. Writing in the Lancet they reported that just 0.4 people per 10 million in the Philippines get such transplants, but in Israel the number shoots up to 506. The report noted both uneven distribution of resources needed to perform the complex procedure and inconsistent support for and participation in donor registries. Niederwieser was quoted in a press release from the journal picked up by ScienceDaily:

“Patients, many of them children, are facing a life and death situation. Ultimately they will die if they cannot get the treatment they need. All countries need to provide adequate infrastructure for patients and donors to make sure that everyone who needs a transplant gets one, rather than the present situation in which access remains restricted to countries and people with sufficient resources.”

What is real with stem cells and joint pain? Bethesda Magazine, the local publication for the county that is home to the National Institutes of Health (NIH), produced a good piece giving the perspective of patients wanting to avoid joint replacement surgery as well as scientists leery of cell-based procedures that have very little evidence to back them up.

The magazine reached out to its neighbor, the NIH to provide some perspective. It quotes Pamela Robey, the co-coordinator of the NIH Bone Marrow Stromal Cell Transplantation Center—those stromal cells are one type of cell often touted by clinics offering to treat joint pain.

“There are a huge number of clinical trials, but there has been next to no published information. The bottom line is there’s no real rigorous data showing it is actually repairing the joint.”

The author also talked to CIRM grantee Larry Goldstein of the University of California, San Diego, in his role as a member of the Ethics and Public Policy Committee of the International Society for Stem Cell Research. He notes that what clinics are offering is unproven and the author directs readers to the ISSCR web site’s “Closer Look” section to get more information on how to evaluate potential therapies they may be considering.

Stem cell stories that caught our eye; progress toward artificial brain, teeth may help the blind and obesity

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.

More progress toward artificial brain. A team at the RIKEN Institute in Japan has used stem cells in a 3-D culture to create brain tissue more complex than prior efforts and from an area of the brain not produced before, the cerebellum—that lobe at the lower back of the brain that controls motor function and attention. As far back as 2008, a RIKEN team had created simple tissue that mimicked the cortex, the large surface area that controls memory and language.

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The Inquisitr web portal wrote a feature on a wide variety of efforts to create an artificial brain teeing off of this week’s publication of the cerebellum work in Cell Reports. The piece is fairly comprehensive covering computerized efforts to give robots intelligence and Europe’s Human Brain Project that is trying to map all the activity of the brain as a starting point for recapitulating it in the lab.

The experts interviewed included Robert Caplan of Tufts University in Massachusetts who is using 3-D scaffolding to build functional brain tissues that can process electrical signals. He is not planning any Frankenstein moments; he hopes to create models to improve understanding of brain diseases.

“Ideally we would like to have a laboratory brain system that recapitulates the most devastating diseases. We want to be able to take our existing toolkit of drugs and understand how they work instead of using trial and error.”

Teeth eyed as source of help for the blind. Today the European Union announced the first approval of a stem cell therapy for blindness. And already yesterday a team at the University of Pittsburg announced they had developed a new method to use stem cells to restore vision that could expand the number of patients who could benefit from stem cell therapy.

Many people have lost part or all their vision due to damage to the cornea on the surface of their eye. Even when they can gain vision back through a corneal transplant, their immune system often rejects the new tissue. So the ideal would be making new corneal tissue from the patient’s own cells. The Italian company that garnered the EU approval does this in patients by harvesting some of their own cornea-specific stem cells, called limbal stem cells. But this is only an option if only one eye is impacted by the damage.

The Pittsburgh team thinks it may have found an unlikely alternative source of limbal cells: the dental pulp taken from teeth that have be extracted. It is not as far fetched at it sounds on the surface. Teeth and the cornea both develop in the same section of the embryo, the cranial neural crest. So, they have a common lineage.

The researchers first treated the pulp cells with a solution that makes them turn into the type of cells found in the cornea. Then they created a fiber scaffold shaped like a cornea and seeded the cells on it. Many steps remain before people give up a tooth to regain their sight, but this first milestone points the way and was described in a press release from the journal Stem Cells Translational Medicine, which was picked up by the web site ClinicaSpace.

CIRM funds a project that also proposes to use the patient’s own limbal stem cells but using methods more likely to gain approval of the Food and Drug Administration than those used by the Italian company.

Stem cells and the fight against obesity. Of the two types of stem cells found in your bone marrow, one can form bone and cartilage and, all too often, fat. Preventing these stem cells from maturing into fat may be a tool in the fight against obesity according to a team at Queen Mary University of London.

The conversion of stem cells to fat seems to involve the cilia, or hair-like projections found on cells. When the cilia lengthen the stem cells progress toward becoming fat. But if the researchers genetically prevented that lengthening, they stopped the conversion to fat cells. The findings opens several different ways to think about understanding and curbing obesity says Melis Dalbay one of the authors of the study in a university press release picked up by ScienceNewsline.

“This is the first time that it has been shown that subtle changes in primary cilia structure can influence the differentiation of stem cells into fat. Since primary cilia length can be influenced by various factors including pharmaceuticals, inflammation and even mechanical forces, this study provides new insight into the regulation of fat cell formation and obesity.”

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

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

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

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

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

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

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

Pressure results in release of a cell signal shown in red

Pressure results in release of a cell signal shown in red

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.