Museum exhibit explaining stem cell super heroes opens in Canada today, due in California in 2016

7108285_origAn international touring exhibit using super hero cells as guides to explain the many roles of stem cells in our lives opens today at the Sherbrooke Museum of Nature and Science in Canada. Its five-year tour will include further displays in Canada, the United Kingdom and three stops on California—the San Francisco Bay area, Los Angeles and San Diego—in 2016.

Super Cell logoDesigned for the general public, with a special eye to children, the exhibit uses hands-on and interactive modules to show just how important stem cells are not only to our early development but also to our daily lives. CIRM was a partner in the development of the exhibit, but the primary mover behind it has been Canada’s Stem Cell Network, and within the network, Lisa Willemse who has really pushed its two-year gestation.

The earliest steps in the development involved visits to children in schools to tease out their points of interest. In a press release she explained some of what they learned:

“How does a lizard grow a new tail? Where does disease come from? How do we start little and get big? These were the kinds of questions the kids asked us, which shows a real interest in the mysteries of the body—mysteries that are largely the domain of stem cells.”

“Much of it is easy to explain, once they understand that stem cells have the ability to make all the kinds of cells in the body. For example, you can tell them that every second, stem cells in your bone marrow make about 2 million new red blood cells. You snap your fingers, and just like that, another 2 million cells were made. Soon they all start snapping their fingers, knowing that every time they do it, something remarkable and vital to life has happened in their own body.”

In Canada, the four modules have explanations in English and French. In California, they will be in English and Spanish. In Spanish the exhibit title “Super Cells: The Power of Stem Cells” becomes Celulas Fantasticas: El Poder Del Las Celulas Madre. I love the concept of a mother cell.

Additional partners in the project included the Centre for Commercialization of Regenerative Medicine in Canada and the UK’s Cell Therapy Catapult.

Don Gibbons

Stem cell stories that caught our eye: a good review at the NY Times, expanding cord blood and leukemia

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

Review paints picture of the field today.
A writer I have respected for many years, Karen Weintraub, wrote a nice review of the current state of stem cell clinical trials in the Tuesday Science Times in the New York Times. She discusses the steady, methodical progress being made:

“Researchers have been slowly learning how to best use stem cells, what types to use and how to deliver them to the body — findings that are not singularly transformational, but progressive and pragmatic.”

She quotes our senior VP Ellen Feigal about the safety seen so far in clinical trials and notes that CIRM should have 10 clinical trials enrolling patients by the end of the year. She also covers the dangers of clinics offering unproven therapies and the power of using iPS-type stem cells to model diseases in the laboratory. Overall, a nicely balanced piece.

Making mitochondrial disease and 3-parent embryos personal. A little newspaper in Oregon called the Willamet Week has published a story that makes the issues around so-called “three-parent” babies very personal. The controversial procedure aims to allow women with rare mitochondrial diseases to have normal children.

Mitochondria, known as the powerhouses of the cell, have the unusual trait of being the only part of the cell besides the nucleus to have any DNA. It is these few genes in the mitochondria that we inherit solely from our mothers because when the DNA from the egg and sperm fuse, the mother’s mitochondria stay in the fluid outside the nucleus. So, to avoid passing along faulty mitochondrial genes, a team in Oregon devised a way to insert the DNA from the mother’s nucleus into a donor egg that had its nucleus removed, a process called nuclear transfer.

Guided by a microscope researchers insert the nucleus from one woman into the egg of another

Guided by a microscope researchers insert the nucleus from one woman into the egg of another

The paper provides a long read—nearly 4,000 words—that goes into great detail about the procedure, the ethics, the research team’s views on the ethics, and the personal story of a patient living with a disease of exhaustion she calls “mitochondrial crash.” The writer lets the patient have the last word on ethics:

“To me it’s win-win because you’re not messing with God’s child. You’re just taking out the bad parts. I don’t want to pick out a blond-haired, blue-eyed tall kid, picking your child’s traits, but to rule out a potentially lethal chronic illness brings in a whole different story.”

Cord blood might now save more adult cancer patients.
Umbilical cord blood is a literal lifesaver for many pediatric cancer patients allowing them to withstand harsh chemotherapy and be rescued by the stem cells in the cord blood. But the procedure is used in few adults because the vast majority of cord blood samples don’t have enough stem cell for an adult requiring the use of two cord samples and doubling the chance for potentially deadly immune reactions.

A team at the University of Montreal screened more than 5,000 molecules looking for one that would let them expand the number of stem cells from one sample in the lab. They hit upon one that they say could allow a 10-fold increase in the number of single cord samples suitable for adults. They expect to begin clinical trials in December.

Science News ran a brief review of the work and the blog Science 2.0 ran the university’s press release with a bit more detail.

Trial begins with cancer drug named for CIRM
Researchers at the University of California, San Diego, announced this week that they had begun a clinical trial with leukemia patients using a drug named for our agency cirmtuzumab. This molecule, in the class of drugs called antibodies, disables a protein that cancer stem cells use to accelerate the growth of cancer.

This trial, for patients with recurrence of their chronic lymphocytic leukemia, became the third CIRM funded team this month announcing plans to start clinical trials. In addition to our blog post the San Diego Union Tribune wrote about the latest trial, and we issued press releases on the trials for spinal cord injury and diabetes.

Don Gibbons

New formula a more efficient way to reprogram adult cells to become like embryonic stem cells

Shinya Yamanaka won the Nobel Prize for developing a recipe of genetic factors that can turn back the clock of adult cells and make them behave like embryonic stem cells. But he would be the first to tell you his recipe ultimately may not be the best one for making these stem cells called iPS cells.

Virtually from the day he published his groundbreaking work, teams around the world have tried to develop new formulas that get around some problems with the original. One issue is the low efficiency of getting true stem cells. Another is the high rate of genetic aberrations that can be produced in the resulting stem cells.

Now, a team pairing researchers at the Hebrew University in Jerusalem and the Whitehead Institute in Cambridge, Massachusetts, has published a new recipe that seems to yield many more true stem cells, ones that are called pluripotent because they can make all cell types. The new cells also seem to have fewer genetic alterations, which could make them safer for clinical use in people.

They made the improved cells by moving from OSKM to SNEL—from the original genetic factors, Oct4, Sox2, Klf4 and Myc, to Sall4, Nanog, Esrrb and Lin28. An elaborate computer analysis of the function of genes helped them come up with the formula.

This work used mouse cells, so up next on their agenda is coming up with a similar formula that works in human cells. HealthCanal ran the university’s press release and Genetic Engineering & Biotechnology News ran a slightly more technical analysis of the work.

Don Gibbons

Stem cell stories that caught our eye: heart stem cells, lizard tails and mapping progress in the field

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.

Could cells in arteries be elusive heart stem cells?
Our hearts have a modest limited ability to regenerate and repair themselves, suggesting we must have a few heart stem cells. But no one has figured out where those cells hang out. Now, a team at Vanderbilt in Nashville has shown that cells in the lining of the heart’s arteries can contribute to new heart muscle.

They made the discovery using a labeling technique that let them tag those cells, called endothelial cells, and show that the same tag showed up in new muscle in the heart. This suggests those cells have the properties of heart stem cells.

The finding also suggests that coronary heart disease, where plaque builds up inside the arteries, could damage the heart with a one-two-punch. Besides narrowing the artery it may also make it more difficult to mobilize these heart stem cells that reside inside the artery lining. The research published in Cell Reports was written up by Genetic Engineering & Biotechnology News.

Secrets of the lizard’s tail. Most folks who have spent any time watching nature programing on TV have seen the handy trick of the green anole lizard. If a predator catches it by the tail it can shed its tail and grow a new one. A team at Arizona State University has uncovered the genetic recipe for how the lizard pulls off this trick.

anole_5They analyzed various segments of tails as they were regrowing to see which genes were turned on that would not normally be turned on in adult tissue. They identified 325 genes. The beauty of the finding is 302 of those genes have matching genes in humans. Those genes become immediate candidates for research into finding ways to allow humans to regrow lost or damaged tissue.

Discover did a nice job of explaining how this lizard is a better model for human comparisons than other animals such as salamanders and fish that can also regrow body parts but use a very different process. And the university press release offers a bit more detail of what the team did.

Review maps where the field is going. Six leaders in the stem cell field wrote a review in the journal Science this week of what to expect in the next few years from research with pluripotent stem cells—those stem cells that can become any tissue in the body, both embryonic stem cells and reprogrammed iPS type stem cells. The authors included researchers from the University of Rochester, the University of Pittsburgh, Harvard, and the University of Wisconsin.

The main hurdles researchers are working to overcome involve maturing the stem cells to the right adult tissue, making sure they are purely those cells, and getting them to integrate with the patient’s own tissue after transplant. They note progress is each of these areas, but in most cases much more work needs to be done.

The University of Rochester put out a press release detailing their faculty member’s contribution to the paper focusing on neural diseases. He suggests that complex diseases that impact multiple types of cells, such as Alzheimer’s, would be the most difficult to treat with stem cells. But diseases impacting a single type of nerve cell, such as Huntington’s, Parkinson’s and multiple sclerosis would be the first to benefit from cells generated from pluripotent stem cells. HealthCanal picked up the university’s release.

Don Gibbons

Tiny transparent zebra fish yields big clue to black box of Alzheimer’s disease

The PR folks at the Flanders Institute for Biotechnology in Belgium produced an unusual press release to describe recent work there published in Developmental Cell. They devoted the first half to the marvels of their animal model the zebra fish.

zebrafish1For those who have only seen these nearly transparent little guys in a home aquarium the story provides a nice explanation for why they are such popular lab models. It is not unusual to walk into a lab with dozens of small fish tanks holding thousands of zebra fish. A couple key reasons: their DNA matches 90 percent of ours and the guys reproduce quickly, just three months after birth.

Nerve stem cells, key players to brain development in the embryo, become few in number in adults. More important, those few we have left seem to be less active when we need them most, when Alzheimer’s disease or other neurodegenerative disease destroys some of our existing nerves. Evgenia Salta at the Institute used the fish to try to discern why.

We have known for some time that the genes in a pathway known as Notch regulate the ability of nerve stem cells to mature into adult nerves. But we don’t know why that goes awry in disease. She focused on a genetic regulatory molecule called a microRNA that is known to be in abnormally low supply in cells from patients with Alzheimer’s.

When they manipulated the fish to lower the levels of this microRNA, the nerve stem cells in the fish failed to mature properly into nerve cells. In the press release published on ScienceDaily Salta is quoted saying:

“To our surprise, the reduced activity of miRNS-132 in the zebra fish blocks the further ripening of the stem cell into nerves cells. This new knowledge about the molecular signaling pathway that underlies this process gives us an insight into the exact blocking mechanism. Thanks to this work in zebra fish, we can now examine in detail what exactly goes wrong in the brains of patients with Alzheimer’s disease.”

You can read about CIRMM-funded projects seeking solutions to Alzheimer’s Disease on our fact sheet.

Don Gibbons

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


It’s always nice to start the week off with some good news and we got this week off to a great start with some great news. ViaCyte has been given the green light to start a clinical trial with its therapy for type 1 diabetes, a program we are funding.

ViaCyte applied to the Food and Drug Administration for approval in mid-July, a process that can sometimes take months. They got their approval in a matter of weeks, which, considering the device they are using is so novel and complicated, is a really significant achievement.

As the Chairman of our governing Board, Jonathan Thomas, J.D., Ph.D., noted in a press release we sent out about the news:

“This is a therapy that we have funded from its earliest days so it’s exciting to see that it is now ready to start a First-in-Human trial. Reaching this milestone is a tribute to years of hard work by the team at ViaCyte, but also to the vision of the people of California who created the stem cell agency to support work like this. That vision is one step closer to being realized.”

So what is this new approach that ViaCyte is trying? Well, in type 1 diabetes the pancreas no longer produces the insulin our bodies need to regulate blood sugar levels. That can increase your risk of heart disease, stroke, kidney failure, blindness, even death. ViaCyte has developed a thin plastic pouch, containing an immature form of pancreatic cells, to mimic the blood glucose regulating function of the pancreas. When the device is implanted under the skin these cells are designed to become the insulin-producing and other cells needed to regulate blood glucose levels. It is believed that these cells will be able to sense when blood glucose is high, and then secrete insulin to restore it to a healthy level.

It’s fascinating science but more than that, it’s a really promising program that has the potential to end reliance on daily testing and injections of insulin for people with type 1 diabetes. It could dramatically change their lives.

Of course this is just one step along the way and, encouraging as it is, it is also important to place it in context. This is the first time it’s being tried in people. In all the pre-clinical testing it’s looked promising, but this is the only test that really counts, seeing if it works in patients with type 1 diabetes. Now we get to find out.






Grafted Stem Cells Snake through Spinal Cord, CIRM-Funded Study Finds

New research lends increasing support to the notion that paralysis may not be so permanent after all.

Scientists at the University of California, San Diego have generated stem cells that, when grafted onto the injured spines of rats—traverse through the injury sites, coupling with nerve cells hidden beneath the damaged tissue. These results, published today in the journal Neuron, are a critical next step towards using stem cell-technology to reverse spinal cord injury—a condition that has long been considered irreversible.

The extension of human axons into host adult rat white matter and gray matter three months after spinal cord injury. [Credit: UCSD School of Medicine

The extension of human axons into host adult rat white matter and gray matter three months after spinal cord injury. [Credit: UCSD School of Medicine]

This research team, led by CIRM grantee Dr. Mark Tuszynski, generated stem cells from the skin cells of an adult human male. These so-called induced pluripotent stem cells, or iPS cells, then had the ability to transform into virtually any cell type. With a bit of coaxing, the team transformed them one more time—into early-stage neurons—and grafted them onto the injured rats. After monitoring the animals over a period of three months, what they began to see astonished them.

The most amazing changes came from the cells’ axons—long, spindly projections that connect neurons to each other, allowing them to communicate through transmission of electrical signals. Much to their surprise, the team saw these iPS cell-derived axons began to grow—some extending across the animals’ entire central nervous system.

But it wasn’t just the fact that the axons grew that excited researchers—it’s where they went. They began to pierce through the spinal injury sites, penetrating scar tissue and grey matter and forming connections with existing rat neurons that had been entombed inside. Even more incredibly, the native rat axons began to do the same—growing and piercing through the iPS cell grafts to form connections of their own.

As Tuszynski explained in a news release:

“These findings indicate that intrinsic neuron mechanisms readily overcome the barriers created by a spinal cord injury to extend many axons over very long distances, and that these capabilities persist even in neurons that have been reprogrammed.”

The results of this study are encouraging, say the research team, though they do raise a few questions about the underlying signaling mechanisms that are guiding these axons to grow and become intertwined. Tuszynski elaborated:

“The enormous outgrowth of axons to many regions of the spinal cord and even deeply into the brain raises questions of possible side effects if axons are mis-targeted. We also need to learn if the new connections formed by axons are stable over time, and if implanted human neural stem cells are maturing on a human time frame—months to years—or more rapidly.”

The researchers are now exploring whether using different types of stem cells, such as embryonic stem cells, would yield similar results. Once they hone in on the best method, they hope to take their findings further down the path towards clinical trials.

“Ninety-five percent of human clinical trials fail,” explained Tuszynski. “We want to determine as best we can the optimal cell type and best method for human translation so that we can move ahead rationally and, with some luck, successfully.”

Research points to another path toward giving diabetics the insulin-producing cells they need

Type 1 diabetes is such a life-changing illness that scores of teams around the world are looking for ways to replace the insulin-producing pancreatic cells that are destroyed in the disease.

Many of these researchers use stem cells of various types to try to generate large quantities of insulin producing cells that could be transplanted. But a few are trying to directly reprogram other pancreas cells into desired beta cells. Often called transdifferentiation, this process could be a great shortcut to getting the needed cells.

Fred Levine and his CIRM-funded colleagues at the Sanford-Burnham Medical Research Institute in La Jolla have succeeded in causing this identity change using a single peptide, which you can think of as a very small protein. The islet cells in our pancreas contain beta cells and alpha cells in close proximity. When a diabetic’s immune system destroys the insulin-producing beta cells it does not harm the alpha cells, so they are a ready supply of cells that could be reprogrammed that are already in the right location. Levine’s team did this with the peptide caerulein. In a press release Levine noted:

“We have found a promising technique for type 1 diabetics to restore the body’s ability to produce insulin. By introducing caerulein to the pancreas we were able to generate new beta cells—the cells that produce insulin—potentially freeing patients from daily doses of insulin to manage their blood-sugar levels.”

Injecting the peptide worked in both a mouse model of diabetes and in human pancreas tissue from cadavers. But it also caused enough inflammation of the pancreas that the team is now tracking down the molecular target where the peptide does its magic. With that knowledge they hope to develop a more specific drug without the side effect.

Levine is well aware that a second step would be needed to protect any new beta cells they create from immune system attack. In a video that the institute produced a collaborator talked about preliminary work to prevent this immune rejection [starting at 2:45 into the video]. She is trying to super charge the type of immune cell called T-regulatory cells that are responsible for maintaining a balanced immune response.

The team published their work online in Cell Death and Disease, July 31.

Don Gibbons

Making stem cells feel like they are growing in the right neighborhood may be key to success

An adage in real estate says that the most important thing is neighborhood, neighborhood, neighborhood. Researchers are learning that the same may be true for stem cell therapies. If you want to mature stem cells into the right adult tissue and get them to behave the way you want, you better pay attention to the environment where they are grown in the lab—before they are transplanted into people.

Two journal articles posted online this month provide good reasons to head the realtors’ advice. CIRM-grantee Shyni Varghese at the University of California, San Diego, provides an elegantly simple example. When trying to turn embryonic stem cells into bone researchers often embed them inside a hydrogel scaffold. This helps them to stay put when transplanted. But researcjers generally rely on chemical or genetic signals to get the stem cells to mature into bone. This results in a mixed population of bone cells and fat cells because both those cell types branch from the same maturation pathway.

Varghese’s team altered the scaffold to make it seem more like the neighboring bone cells the maturing stem cells would encounter in normal bone. They mineralized it with calcium and phosphate. And when they did, they got pure bone cells in the lab dish. What’s more, when they implanted those “tissues” into animals, they formed densely calcified bone—the hard kind we want. The team published the work in the Journal of Materials Chemistry online July 4.

A review article in the journal BioResearch provided a good overview of ways various groups have tried to precondition stem cells in the lab so that they will survive after transplant. One of the biggest stumbling blocks in the field remains the difficulty of getting stem cells to survive in the patient, whether those are humans or little mouse patients. It turns out from the research cited in this review that turning the lab growth environment into something more closely resembling the environment in the patient improves survival.

Stem cell researchers need their version of the Google mapping bike to reveal the natural neighborhoods where the cells would grow.

Stem cell researchers need their version of the Google mapping bike to reveal the natural neighborhoods where the cells would grow.

They looked at several aspects of typical lab cell cultures that don’t mimic real tissue. Sites of injury where stem cells are needed often are also sites of lowered oxygen levels, inflammation and a disruption of the normal cell-to-cell contact that helps guides cell behavior. They found that adjusting each of those in the lab resulted in cells that were more likely to survive after transplant.

Most notably, when they grew cells in aggregates that restored cell-to-cell contact—restored the sense of neighborhood—cell survival improved significantly. Genetic Engineering & Biotechnology News wrote a brief summary of the work.

Don Gibbons

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

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

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

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

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

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

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

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

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

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

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

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

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

Don Gibbons