Stem cell stories that caught our eye: multiple sclerosis, virus genes in embryos and preventing cancer’s spread to the brain

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.

Drugs activate brain stem cells in MS. We have frequently written that in some situations our own stem cells may do a better job at repairing the body than transplanted cells. A team at Case Western in Cleveland has done just that with lab and animal models of Multiple Sclerosis (MS). Even better, they did it with drugs that are already approved for other uses.

They used a steroid, clobetasol, and an antifungal, miconazole, to get a type of stem cell found in the brain to more effectively produce the myelin sheets that protect our nerves and that get destroyed in MS. But in a story in Science Blog the researchers cautioned that patients should not go ask a doctor to inject those drugs. They are currently used only as topical agents on the skin and no one knows what they would do internally in people.

“Off-label use of the current forms of these drugs is more likely to increase other health concerns than alleviate multiple sclerosis symptoms. We are working tirelessly to ready a safe and effective drug for clinical use,” said Paul Tesar who led the study.”

Specifically, the team worked with stem cells called oligodendrocyte progenitor cells. Growing them in the lab they tested hundreds of approved drugs to see if any would nudge those cells into producing myelin. They found these two and tested them in a mouse model of MS and saw improved function in the mice. They are now looking to test other drugs hoping to find one safe for internal use in humans.

Viral genes active in early embryos. Virus genes, mostly left over from infections of our ancestors thousands of years ago, make up some eight percent of the genetic material in our chromosomes. In general those genes just sit there and don’t do anything. But a CIRM funded team at Stanford has found that in the early days of embryo development some of them become quite active.

In fact, they seem to commandeer the growing embryo’s cellular machinery to produce whole virus particles that the researchers detected in the interior of the cells. What they could not determine is whether that activity is benign or somehow directs the development of the embryo—or might be the virus reasserting its parasitic ways.

“It’s both fascinating and a little creepy,” said Joanna Wysocka, the senior author on the study that appeared this week in Nature. “We’ve discovered that a specific class of viruses that invaded the human genome during recent evolution becomes reactivated in the early development of the human embryo, leading to the presence of viral-like particles and proteins in the human cells.”

In the press release, Stanford’s Krista Conger does a nice job of laying out some of the prior research about the origins and nature of all the viral genes hidden amongst our DNA. The release, picked up by HealthCanal makes it clear the finding raises more questions than it provides answers. Edward Grow, the graduate student who was first author on the paper put it this way:

“Does the virus selfishly benefit by switching itself on in these early embryonic cells? Or is the embryo instead commandeering the viral proteins to protect itself? Can they both benefit? That’s possible, but we don’t really know.”

Stem cells with multiple genetic tricks fight cancer. Breast cancer wreaks the most havoc when it spreads and about a third of the time it spreads to the brain. To fight that insidious spread a team a Massachusetts General Hospital and the Harvard Stem Cell Institute has rigged nerve stem cells with multiple genetic tricks to prevent breast cancer cells from growing after they get to the brain.

Certain types of nerve stem cells are naturally attracted to tumors. So the team led by Khalid Shah genetically manipulated those stem cells to express a gene called TRAIL. That gene produces a protein that activates a receptor on the surface of cancer cells that causes them to self-destruct. Then to make sure those stem cells did not stick around and multiply when they are no longer needed, the researchers added another gene that made them susceptible to a common antiviral drug. That drug could be given once the cells had done their work of delivering the suicide note to the cancer cells and the stem cells themselves would then be eliminated.

A press release on the work from MGH was picked up by ScienceNewsline and quoted Shah on the significance of the findings:

“Our results are the first to provide insight into ways of targeting brain metastases with stem-cell-directed molecules that specifically induce the death of tumor cells and then eliminating the therapeutic stem cells.”

In order to measure their results the team started with yet another genetic trick. They wanted to make sure the loaded stem cells were getting to the tumors. So, before they injected breast cancer cells into the carotid arteries in the necks of mice, they modified the cells so that they would express fluorescent markers. That glow could be tracked allowing the researchers to monitor the disappearance of the cancer cells.

This mouse work is obviously many steps away from use in humans, but it provides an ingenious path to follow.

Stem cell stories that caught our eye: iPS cells guide ALS trial, genetic link to hearing loss and easier to use stem cell

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.

An ALS clinical trial with a twist.
It is well known that the disease we call ALS, or Lou Gehrig’s Disease, behaves differently in different people, so it makes sense that a potential medication might help some people more than others. Now a collaborative group in the North East wants to use iPS-type stem cells to predict who will respond to a medication at the outset of a clinical trial.

The drug to be tested is already used to calm hyper excitable nerves in people with epilepsy. Hyper excitable nerves also seem to play a role in ALS, at least in some patients. So the team, lead by a researcher at Massachusetts General Hospital with others from Harvard, the Northeast ALS Consortium and GlaxoSmithKline, will reprogram the patients’ blood cells to be iPS type stem cells and grow them into nerve cells in the lab and test their response to the drug, Retigabine.

The ALS Association is providing part of the funding for the effort, and the association’s chief scientist, Lucie Bruijn noted the unique nature of this effort in the association’s press release picked up by Bloomberg.

“This powerful collaboration of leaders in the fields of stem cells, clinical neurology, ALS research and GSK will be the first time that lab data from patient derived stem cells with disease-specific properties that respond to drugs have formed the basis for a clinical trial.”

Do stem cells prefer wearing a coat? One of our grantees and the editor of the journal Stem Cells, Jan Nolta, likes to refer to mesenchymal stem cells as little ambulances that run around the body delivering first aid supplies. These cells found in bone marrow and fat are being tested in many different disease, but in most cases they are not expected to actually make repairs themselves. Instead researchers use them to deliver a variety of protein factors that trigger various components of the body’s natural healing machinery.

Mesenchymal stem cells captured in microcapsules

Mesenchymal stem cells captured in microcapsules

One problem is the cells often do not stick around very long delivering their needed medical supplies. A team at Cornell University in New York thinks they may have found a way to improve the performance of these stem cells, by giving them a coat. By enclosing the stem cells in a capsule the cells stay in place better and more effectively help wounds heal, at least in the lab model the team used.

The university’s press release was picked up by Medical Design Technology.

Noise plus bad genes bad for hearing. Some people can spend years of Saturday nights attending loud rock concerts and have no issue with their hearing. Others end up constantly adjusting the battery on their hearing aids. A CIRM-funded team at the University of Southern California thinks they have fingered a genetic explanation for the difference.

Hearing is a complex process involving many components, which has resulted in no clear answers from previous attempts to find genetic links to hearing loss. The USC team performed a more complex analysis known as a GWAS, genome-wide association study. The result provided strong evidence that variations in the gene Nox3, which is normally turned on only in the inner ear, account for the differences in susceptibility.

Researchers now have a clear target to look for opportunities for prevention and therapy. Futurity picked up the University’s press release.

Accident creates new type of stem cell.
Much of the work with embryonic stem cells centers on figuring out what proteins and other factors to expose them to in order to get them to mature into a desired type of cell. One such attempt at the University of Missouri resulted in creating a new type of stem cell that may be easier to work with than embryonic stem cells (ESCs).

They call their new cells BMP-primed stem cells because one of the various factors they were adding to their ESCs in a lab dish was Bone Morphogenetic Protein. Michael Roberts, the leader of the team, described the potential value of the new stem cells in an article in Genetic Engineering & Biotechnology News:

“These new cells, which we call BMP-primed stem cells, are much more robust and easily manipulated than standard embryonic stem cells. BMP-primed cells represent a transitional stage of development between embryonic stem cells and their ultimate developmental fate, whether that is placenta cells, or skin cells or brain cells.”

For hardcore biologyphiles, the new cells offer a chance to better understand the early stages of embryo development. ESCs can form any part of the body but they cannot form the placenta and other early tissues needed to support the embryo. The BMP-primed stem cells can. So they may yield some long-sought answers about what determines cell fate in the early days after fertilization and perhaps some practical information on diseases related to the placenta like pre-eclampsia.

Stem cell stories that caught our eye; converting bad fat to good, Parkinson’s and X-linked 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.

Which fat for you, white, brown or beige.
Those who read up on those pesky fat cells that accumulate in our bodies probably have heard about white fat and brown fat. White is the bad guy linked to obesity and diabetes and brown is the good guy that burns energy and fosters leanness. Add one more color. A team at the University of California, San Francisco, has isolated beige fat that can convert white to brown.

body fatThey now want to see if they can figure out the molecular mechanism behind this conversion to see if they can develop a therapy to combat obesity. I heard a presentation on similar work at the International Society for Stem Cell Research last June, and there were suggestions that the stem cell known to reside in fat may play a role, but no one seems to be sure.

The current research made it into Nature Medicine and ScienceDaily picked up the university’s press release, which quotes the senior researcher, Shingo Kajimura:

“This finding brings us another step closer to the goal of our laboratory, which is engineering fat cells to fight obesity. We are trying to learn how to convert white fat into brown fat, and until now, it had not been demonstrated that this recruitable form of brown fat is actually present in humans.”


A wonkish revelation on reprogrammed stem cells.
When Shinya Yamanaka first discovered how to reprogram adult cells into embryonic-like stem cells, the resulting iPS cells won him the Nobel Prize. But neither he nor anyone else knew exactly how this reprogramming actually happened. It was assumed that by adding genes that are normally only active during embryo development we were turning back the clock and letting the cells sort of start over.

Now, CIRM-funded researchers at Stanford have discovered the cells first go through a clearly identifiable intermediate state that does not have any of the markers of early stem cells, so called pluripotency genes. The leader of the team, Marius Wernig, described his surprise in a university press release picked up by HealthCanal:

“This was completely unexpected. It’s always been assumed that reprogramming is simply a matter of pushing mature cells backward along the developmental pathway. These cells would undergo two major changes: They’d turn off genes corresponding to their original identity, and begin to express pluripotency genes. Now we know there’s an intermediary state we’d never imagined before.”

The research, published in Nature, used a clever new technique that lets cells grow in individual tiny wells on a laboratory plate. Wernig hopes the finding will help his group and others find ways to improve reprogramming efficiency, which is commonly in single percentage points and rarely in the teens.

Chemical trick yields nerves needed in Parkinson’s.
It’s relatively easy to get stem cells to mature into nerves, but can be quite difficult sometimes to get them to grow into just the right kind of nerves. The dopamine-producing nerves needed in Parkinson’s disease turn out to be one of the difficult ones.

Now, a team from Brazil has used an approved drug to treat stem cells in the lab and get them to consistently mature into dopamine-producing nerves. What’s better, the cells survived and continued to produce dopamine for 15 months after being transplanted into mice. ScienceDaily picked up the press release from D’Or Institute for Research and Education.

The X chromosome and disease? Researchers have long sought answers to why when a disease gene resides on the X chromosome, it often causes more harm in boys than girls. A likely culprit is the process a developing embryo uses to shut down one of the two X chromosomes in females, and a team at Stanford thinks they have found a way to discover how.

The CIRM-funded team lead by Howard Chang used a new molecular tool to study in detail all the components of the cell involved in silencing one of the X chromosomes.

Calico cats are female due to X-chromosome silencing.

Calico cats are female due to X-chromosome silencing.

Researchers have known for some time that one particular genetic component, an RNA called Xist, plays a lead role. But Chang’s team discovered 80 different proteins it interacts with in order to completely shut down one X chromosome. They hope that learning more about the process will let researchers figure out how this selective silencing protects females from some of the mutations on the X chromosome.

The Stanford press release, picked up by HealthCanal, starts with a fun explanation of X silencing and how it can lead to calico female cats, but not males—sorry Garfield you don’t exist.

Stem cell stories that caught our eye; creating bone, turning data into sound, cord blood and path of a stem cell star

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.

A better ratio of bone to fat
. Most of us at any age would prefer a little less fat and older folks, particularly ones plagued by the bone loss of osteoporosis, could use a bit more bone. Since both types of tissues come from mesenchymal stem cells (MSCs) a team at the University of Miami decided to look for chemical triggers that tells those stem cells whether to become fat or bone.

They found an enzyme that seems to do just that. In mice that were born with a mutation in the gene for that enzyme they saw increased bone growth, less fat production and a leaner body mass. HealthCanal picked up the university’s press release that quoted the leader of the team Joshua Hare:

“The production of bone could have a profound effect on the quality of life for the aging population.”

He goes on to note that there are many hurdles to cross before this becomes a therapeutic reality, but the current work points to lots of potential.

Path to becoming a star stem cell scientist. D, the city magazine for Dallas, published a lengthy—nearly 4,000-word—feature on Sean Morrison, one of the undisputed leaders of our field. While it starts out talking about his latest role of creating a multi-pronged center for innovation at

Sean Morrison

Sean Morrison

Children’s Medical Center Dallas and UT Southwestern, it spends most of its words on how he got there.

It’s fun reading how someone gets into a field as new as stem cell science and what keeps them in the field. Initially, for him it seems to originate from an immense curiosity about what was not known about the powerful little stem cells.

“Fifteen years ago, there was nothing known at the molecular level about how stem cells replicate. And I really felt it was a fundamental question in biology to understand. It was a question that was central to a lot of important issues, because the ability of stem cells to self-renew is critical to form your tissues throughout development, to maintain your tissues throughout adulthood.”

There is also a good retelling of Morrison’s role in the protracted and hard-fought battle to make embryonic stem cell research legal during his years in Michigan. He started working on the campaign to overturn the ban in 2006 and in 2008 the voters agreed. The article makes a compelling case for something I have advocated for years: scientists need to practice speaking for the public and get out and do it.

Turning stem cell data into sound. Interpreting scientific data through sound, sonification, is a bit trendy now. But the concept is quite old. Think of the Geiger counter and the speed of the click changing based on the level of radiation.

Researchers tend to consider sonification when dealing with large data sets that have some level of repetitive component. Following the differentiation of a large number of stem cells as they mature into different types of tissue could lend itself to the genre and a team at Cardiff University in Scotland reports they have succeeded. In doing just that.

HealthCanal picked up the university’s piece talking about the project. Unfortunately it does a very poor job of explaining how the process actually works. I did find this piece on ocean microbes that describes the concept of sonification of data pretty well.

Cord blood poised for greater use. I get very uncomfortable when friends ask for medical advice around stem cells. I usually try to give a lay of the land that comes short of direct advice. A common question centers on the value of paying the annual storage fees to freeze their baby’s cord blood. To which, I typically say that for current uses the value is marginal, but for the uses that could come in five to 10 years, it could be quite significant.

So, it was not surprising to read a headline on a Scientific American Blog last December reading “Vast Majority of Life-Saving Cord Blood Sits Unused.” But it was also fun to read a well-documented counter point guest blog on the site this morning by our former President, Alan Trounson. He suggested a better headline would be: “Vast Majority of Life-Saving Cord Blood Sits Poised for Discovery.”

He details how cord blood has become a valuable research tool and lists some of the FDA-approved clinical trials that could greatly expand the indication of cord blood therapy. While some of those trials will likely produce negative results, some will succeed and they all will start to show how to turn those frozen vials into a more valuable resource.

Stem cell stories that caught our eye; cystic fibrosis, brain repair and Type 2 diabetes

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.

“Organoids” screen for cystic fibrosis drugs
. Starting with iPS-type stem cells made by reprogramming skin cells from cystic fibrosis (CF) patients a team at the University of Cambridge in the U.K. created mini lungs in a dish. These organoids should provide a great tool for screening drugs to treat the disease.

The researchers pushed the stem cells to go through the early stages of embryo development and then on to become 3-D distal airway tissue, the part of the lung that processes gas exchange. They were able to use a florescent marker to show an aspect of the cells’ function that was different in cells from CF patients and those from normal individuals. When they treated the CF cells with a drug that is being tested in CF patients, they saw the function correct to the normal state.

Bioscience Technology
picked up the university’s press release about the work published in the journal Stem Cells and Development. It quotes the scientist who led the study, Nick Hannon, on the application of the new tool:

“We’re confident this process could be scaled up to enable us to screen tens of thousands of compounds and develop mini-lungs with other diseases such as lung cancer and idiopathic pulmonary fibrosis.”

To repair a brain knock its “pinky” down. A team at the University of California, San Francisco, has discovered a molecule that when it is shut down nerve stem cells can produce a whole lot more nerves. They call the molecule Pnky, named after the cartoon Pinky and the Brain.

Pinky_and_the_Brain_vol1Pkny belongs to a set of molecules known as long noncoding RNAs (lncRNAs), which researchers are finding are more abundant and more important than originally thought. The most familiar RNAs are the intermediary molecules between the DNA in our genes and the proteins that let our cells function. Initially, all the noncoding RNAs were thought to have no function, but in recent years many have been found to have critical roles in determining which genes are active. And Pnky seems to tamp down the activity of nerve stem cells. In a university press release picked up by HealthCanal Daniel Lim, the head researcher explained what happens when they shut down the gene:

“It is remarkable that when you take Pnky away, the stem cells produce many more neurons. These findings suggest that Pnky, and perhaps lncRNAs in general, could eventually have important applications in regenerative medicine and cancer treatment.”

Lim went onto explain the cancer connection. Since Pnky binds to a protein found in brain tumors, it might be involved in regulating the growth of brain tumors. A lot more work needs to happen before that hunch—or the use of Pnky blockers in brain injury—can lead to therapies, but this study certainly paints an intriguing path forward.

Stem cells and Type 2 diabetes. A few teams have succeeded in using stem cells to produce insulin-secreting tissue to correct Type 1 diabetes in animals, but it has been uncertain if the procedure would work for Type 2 diabetes. Type 1 is marked by a lack of insulin production, while resistance to the body’s own insulin, not lack of insulin, is the hallmark of type 2. A team at the University of British Columbia has new data showing stem cell therapy may indeed have a place in treating Type 2.

In mice fed a high fat diet until they developed the symptoms of Type 2 diabetes the stem cell-derived cells did help, but they did not fully correct the metabolism of the mice until they added one of the drugs commonly used to treat diabetes today. The drugs alone, also did not restore normal metabolism, which is often the case with human Type 2 diabetics.

The combination of drugs and cells improved the mice’s sugar metabolism, body weight and insulin sensitivity. The research appeared in the journal Stem Cell Reports and the University’s press release was picked up by several outlets including Fox News.

They transplanted cells from humans and even though the mice were immune suppressed, they took the added measure of protecting the cells in an encapsulation device. They noted that this would be required for use in humans and showing that it worked in mice would speed up any human trials. They also gave a shout out to the clinical trial CIRM funds at Viacyte, noting that since the Food and Drug Administration has already approved use of a similar device by Viacyte, the work might gain more rapid approval.

Stem cell stories that caught our eye; drug screening, aging stem cells in brain repair and blood diseases

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.

Heart-on-a-chip used to screen drugs. With CIRM funding, a team at the University of California, Berkeley, has used stem cell technology to create a virtual heart on an inch-long piece of silicon. The cells in that “chip” mimic the physiology of a human heart and have shown that they can accurately show how drugs will impact the heart.
HeartChip4196107801
Starting with iPS-type stem cells made from reprogramming adult cells the researchers grew them into heart muscle that could beat and align in multiple layers with microscopic channels that mimic blood vessels. They tested three drugs currently used to treat heart disease and found the changes seen in the heart-on-a-chip were consistent with what is seen in patients. For example, they tested isoproterenol, a drug used to treat slow heart rate and saw a dramatic increase in heart rate.

But the real value in the silicon-housed heart will be in screening potential new drugs and finding out adverse impacts before taking them into costly human clinical trials. Genetic Engineering & Biotechnology News wrote up the work and quoted a member of the team, Kevin Healy:

“It takes about $5 billion on average to develop a drug, and 60 percent of that figure comes from upfront costs in the research and development phase. Using a well-designed model of a human organ could significantly cut the cost and time of bringing a new drug to market.”

Brain stem cell activity decreases with age. We have known for some time that the adult stem cells that reside in most of our tissues and spend our lives repairing those tissues are less effective as we age. But the stemness of those cells—their ability to regenerate themselves—has not generally been questioned, rather we have assumed they just lost some of their ability to mature into the type of cell needed to make the repair.

Now, a team at the Ludwig-Maximilians-Universitat in Munich has published data suggesting that brain stem cells over time loose both their ability to renew themselves and some of their ability to become certain kinds of nerves. ScienceDaily picked up a press release from the institution and it quoted one of the authors, Magdalena Gotz, on the implications of their finding for therapy.

“In light of the fact that the stem cell supply is limited, we must now also look for ways to promote the self-renewal rate of the stem cells themselves and maintain the supply for a longer time.”

Another alternative for correcting genetic blood disease. CIRM funds a few programs that are trying to treat blood diseases such as sickle cell anemia and beta thalassemia by genetically altering blood forming stem cells. The goal being to correct defects in the gene for hemoglobin, the protein that carries oxygen in red blood cells.

Instead of starting with a patient’s own blood stem cells, which can require a somewhat traumatic harvest procedure, a new approach by a team at the Salk Institute in La Jolla creates iPS type stem cells by reprogramming the cells in a small skin sample. They mature those into blood stem cells and genetically modify them so that they can produce red blood cells that have the correct hemoglobin.

The Salk team uses a modified cold virus to carry the gene into the cell. ScienceDaily picked up the institute’s press release, which quotes one of the co-first authors on the study Mo Li on how the process works:

“It happens naturally, working like a zipper. The good gene just zips in perfectly, pushing the bad one out.”

CIRM funds other work by the senior author, Juan Carlos Izpisua Belmonte, but not this project. Because you never know which technology is going to work out best in the long term, it is nice to see other funders stepping up and pushing this alternative forward.

Stem cell stories that caught our eye; Parkinson’s, drug boosts stem cells in MS and gender equity in science

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 survive and aid Parkinson’s in monkey.
Ole Isacson, a pioneer in the effort to figure out how to use stem cells to treat Parkinson’s Disease, has published new research that suggests a good option. His Harvard team used nerves grown from reprogrammed iPS type stem cells created from the monkey’s own skin.

Dopamine producing nerves created from skin cells of primates

Dopamine producing nerves created from skin cells of primates

His earlier efforts using nerves grown from embryonic stem cells did not result in production of the dopamine that Parkinson’s patients need. He speculates that this was because they were donor cells and required immune suppression to avoid rejection. With the iPS-derived nerves no immune suppressants were needed and the cells survived two years and reversed much of the Parkinson’s symptoms in the one animal that got that type of cell.

ScienceBlog picked up the university’s press release, which described the therapeutic benefit this way:

Isacson said the conclusion of this experiment marks “the first time that an animal has recovered to the same activity level he had before.” He noted that the animal was “able to move as fast around its home cage” as an animal without Parkinson’s, and had normal agility, though individual motions were still slowed by the disease.

He also cautioned that it would be at least three years before he could do the experiments needed to prove the procedure was safe enough to use in patients.

Nerve cells for memory created from stem cells.
The cerebral cortex is the most complex part of our brains. This large outer layer processes memory, vision and language. Its complexity has always given researcher pause in thinking about ways to use stem cells to repair damage in it. Now, an international team working in Belgium and France has grown cortex nerves in the lab, transplanted them in mice with damaged cortices and seen the nerves survive and integrate into the healthy neighboring tissue.

In these experiments the damaged area in the mice was in the visual cortex and some of the animals did show a return of visual stimulus after the transplants. The researchers published their results in the journal Neuron and Science Daily picked up a release from the Belgium university, Libre de Bruxelles.

Drug gets brain stem cells to do better job. We retain a few brain stem cells throughout our life, but they are often not up to the task of repairing large areas of damage. This is the case in multiple sclerosis when our immune system destroys much of the myelin sheath that coats and protects the nerves.

Using a drug already approved by the Food and Drug Administration for other uses, researchers at the University of Buffalo were able to increase the production of myelin in a mouse model of the disease. The drug targets the middleman cells that are half way between stem cells and mature myelin called oligodendrocyte progenitor cells.

They found the drug by first stepping back to look to see what molecules inside the cell are normally active as the stem cells mature to progenitors and then to myelin. They identified a specific molecular pathway needed for this maturation and then looked for drugs that might impact that pathway. They hit upon solifenacin, an agent used for overactive bladder, which results from activity in that same molecular pathway. They told Genetic Engineering & Biotechnology News that they are now looking for funding to conduct human clinical trails.

Stem cell foundation pushes for gender equality. The New York Stem Cell Foundation launched its “Initiative on Women in Science and Engineering (IWISE)” in February 2014 and this week the journal Cell Stem Cell published the resulting recommendations.

The IWISE working group’s first meeting a year ago resulted in seven actionable strategies to advance women in science, medicine and engineering. The group continued to refine those over the year, met again last month to finalize them prior to publication.

The seven strategies include:
1) Implement flexible family care spending
2) Provide “extra hands” awards
3) Recruit gender-balanced external review committees and speaker selection committees
4) Incorporate implicit bias statements
5) Focus on education as a tool
6) Create an institutional report card for gender equality
7) Partner to expand upon existing searchable databases of women in science, medicine, and engineering

The press release from NYSCF was picked up on the web site ECN and has a quote from former CIRM governing board member, Claire Pomeroy, who is now president of the Lasker Foundation.

“The brain power provided by women in science is essential to sustaining a thriving US society and economy. It is time to move beyond just lamenting its loss and embrace the actions called for in this timely report.”

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.