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.

International stem cell group offers much needed guidance for patients and families

Yesterday the International Society for Stem Cell Research launched a greatly expanded website for the public. While the site, “Closer Look at Stem Cells,” offers a broad overview of stem cell science, the group launched it out of concern stem cell treatments are being marketed by clinics around the world without appropriate oversight and patient protections in place.

closer look webThe design for the new site provides easy navigation that quickly gets you to brief outlines and opportunities for a bit more information one click down. Most important, the detail page often includes a bright yellow warning icon with messages like this:

“View clinics that offer the same cell treatment for a wide variety of conditions or diseases with extreme caution. Be wary of claims that stem cells will somehow just know where to go and what to do to treat a specific condition.”

I could buy several rounds at the pub if I had a dollar for every time I said something like that to a desperate patient or family member who called CIRM with questions.

With quick reads like “Nine things to know about stem cell treatments,” as well as a more in-depth patient handbook the site provides ample opportunities to get the level of information any individual wants. It offers clear explanations for the different phases of clinical trials and what to expect if you enter a clinical trial.

A task force of society members and staff produced the new site. The chair of the task force, Megan Munsie from Stem Cells Australia, noted some of the concerns that triggered the effort in the organization’s press release:

“Promising clinical trials are underway for many diseases and conditions, but most stem cell-based treatments are still in the future. We hope that the website will foster interest and excitement in the science, but also an understanding of the current limitations of stem cells as medicine and a healthy skepticism of clinics selling treatments.”

Hope mixed with a good dose of skepticism is always a good approach to a new field of science. Our web site also offers advice for things to consider if a person is contemplating going to a clinic offering an unproven therapy outside of a clinical trial.

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: Hair stem cells, amniotic fluid cells for repair and fixing kids’ faulty genes

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.

With hair, lose a few to grow more.
A team at the University of Southern California has shown that if you pull out a couple hundred hairs in just the right pattern you could trigger a thousand or more hairs to grow. It is the latest example of several we have written about that show stem cells react very acutely to their environment.

The researcher had known that hair follicle injury affects the adjacent environment and that environment can influence hair growth. They teamed up with a University of California, Irvine, expert on “quorum sensing,” a field that the USC press release defined as “how a system responds to stimuli that affects some, but not all members”. They tested various patterns of hair follicle damage caused by plucking hairs on the back of a mouse. They eventually found the pattern and spacing that turned the 200 hairs loss into a thousand-strand gain.

The stem cells that reside at the base of hair follicles are a common tool for studying stem cell behavior because they are easy to get at. And while this work could eventually produce real cosmetic benefits for folks follicularly challenged like myself, the real payoff could come from finding similar quorum affects in stem cells in other organs, which the senior researcher, Cheng-Ming Chuong, notes in the release picked up by Epoch Times:

“The implication of the work is that parallel processes may also exist in the physiological or pathogenic processes of other organs, although they are not as easily observed as hair regeneration.”

Baby’s amniotic fluid as source of repairs. The amniotic fluid that surrounds a growing baby carries cells shed by the fetus that doctors use to diagnose problems, but it also has some valuable stem cells, actually a few types of stem cells. Even though those cells are characteristically adult stem cells, because they have recently crossed the line from embryo to adult, they seem to be more versatile than adult stem cells, and since they match the baby could be the perfect cell for repairing birth defects.

Mature blood vessels form after two weeks in a mouse, with red blood cells flowing at the bottom right.

Mature blood vessels form after two weeks in a mouse, with red blood cells flowing at the bottom right.

Scientists at Rice University and Texas Children’s hospital have reported that when you seed those stem cells into the gel scaffolds commonly used for tissue engineering, the resulting tissues do a better job of growing blood vessels. And without the nutrients brought by new vessels, repair tissues will not survive. They now hope to use this new technique in their ongoing efforts to grow heart muscle patches for children born with heart defects.

The university’s press release was picked up by ScienceDaily. It looks like the fluid and cells normally thrown away after a prenatal test, might become a valuable resource.

Genetically correcting childhood disease.
Last week Stanford organized a multi-day symposium called Childx with an impressive array of speakers from around the world talking about how to improve child health. It ended with a special session on the rapid advances being made by combining stem cell science and gene therapy.

“It’s not just science fiction anymore,” Stanford’s Matthew Porteus, told the audience. “We can correct mutations that cause childhood disease.”

The university’s Scope blog summed up the session in a post this week. It discusses progress in sickle cell anemia, severe combined immune deficiency (SCID) and epidermolysis bullosa, among others. The piece also has a voice from industry cautioning that many hurdles remain before any of these therapies can be scaled up to broad use.

But my email this morning had a potent reminder that enough scientists are getting on this bandwagon to make it happen. The subject line of a sales pitch was “Boost transduction with 20 % off Lentiviral Particles,” which referred to the viral units used to carry genes into cells hoping they with take up residence there and function, aka transduction.

CIRM has bet big on this avenue of research investing more than $110 million in nine projects that combine stem cells and gene manipulation and are either in the clinic or soon will be. We will be launching a new series of posts on “Genes + Cells” next week.

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.

New understanding of the inner workings of our genetic tool kit should help us make smarter repairs

For young biology students the steps from genes to their function becomes a mantra: DNA makes RNA and RNA makes protein. But it is really not quite that simple. A few different types of RNA act along the path and we are now learning that the structure, or shape, of the individual RNA molecules affects their function.

Which genes succeed in producing their designated protein determines what the cell actually does—what kind of tissue it is and how well it performs the role it is assigned. Switching gene function on and off turns out to be quite complex with players among the molecules that are part of the backbone of DNA as well as the various forms of RNA. We have made great strides in the past decade in understanding the role of those DNA structural components, the so-called epigenetics, but still have major gaps in our understanding of the many roles of RNA.

DNA dogmaWith CIRM-funding, a team headed by Howard Chang at Stanford has gotten around a major hurdle in unlocking this complex issue. Like DNA, RNA is made up of various repeats of four molecules called bases. Prior to Chang’s work researchers could only track the structure of RNA associated with two of those bases. His team modified a commonly used bio-chemical tool called SHAPE to reveal the workings of all four RNA bases in living cells.

The team verified something that is increasingly being shown, static cells frozen in time a lab dish do not necessarily reflect what goes on in living cells. In this study those differences manifest in the structure of the RNA that determines what molecules are next to each other, which impacts their activity. After more than 2 billion measurements of more than 13,000 RNAs in the lab and in living cells, the team quantified those differences and showed how this molecular “folding” changes the function of the various RNAs.

They published the work, for which they used mouse embryonic stem cells, on-line today in Nature. In the closing paragraph of the journal article they speculate on the impact of the new ability to better understand the roles of RNA:

“In the future, viewing the RNA structurome when cells are exposed to different stimuli or genetic perturbations should revolutionize our understanding of gene regulation in biology and medicine.”

Since so many of the research projects that seek to reverse the course of disease try to change the genetic functioning of cells, this new understanding should be able to reduce the number of blind alleys scientist have to go down to get a desired result. It should allow the design of studies based on more logic and less chance, speeding the development of therapies.

Conference provides critical connections between clinical projects and investors

Having a mission like CIRM’s, which calls on us to develop therapies for unmet medical needs, clearly means we cannot sit back and marvel at all the great projects we have in the pipeline. We have to deliver commercial products available to all patients in need. And that cannot be done without additional investors.

The Alliance for Regenerative Medicine (ARM) takes that maxim seriously as well. The international advocacy organization, of which CIRM was a founding member five years ago, will host its third annual RegenMed Investor Day in New York City next Wednesday March 25.
ARM-logo-sm
During the full-day event 32 companies will present their progress to a wide array of investors. Traditional venture capital investors will be represented alongside investors from institutions and multinational pharmaceutical giants.

The day will be rounded out with three panel discussions and two fireside chats with market research analysts, company CEOs and leading clinicians. The fireside chat during lunch will feature CIRM President and CEO Dr. C. Randall Mills who will talk about public-private partnerships making joint investments to bring therapies to patients, and how the revised work plan we call CIRM 2.0 will make it easier for companies to work together with CIRM to advance promising therapies.

Getting just the eleven projects CIRM is funding in clinical trials today through to commercial products will require a broad mix of funding partnerships. With our portfolio and that of the industry as a whole growing rapidly, conferences like this one are critical.

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.