Stem cell stories that caught our eye: fragile X syndrome, turning cancer into fat, and Parkinson’s

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

Stem cells reveal common cause of mental retardation. In science it can be frustrating to know what defect causes a condition, but not know how that defect causes the damage. Researchers have been stuck in that limbo with fragile X syndrome for more than two decades. We have known that this form of mental retardation happens because one gene is repeated hundreds of times, and at some point while the baby is developing, the repeats cause the gene to malfunction and stop producing a needed protein. It turns out to be a middleman problem. The DNA in our genes is read by RNA that in turn makes the needed protein, but in fragile X the RNA reading of DNA gets gummed up like a stuck zipper according to work published today in Science by researchers at Weill Cornell Medical College.

Researchers have never been able to mimic fragile X in mice, because no matter how many extra copies of the gene they cram into the animals, they can’t get the gene to turn off. So, the Cornell team used human embryonic stem cells that had the mutation, which they grew and monitored in the lab for signs of fragile X. This work highlights the value of using pre-implant genetic diagnosis (PGD) to help parents undergoing in vitro fertilization. It allows them to avoid having a disabled child by selecting only healthy embryos for implantation, while at the same time providing researchers with a valuable model of the disease—the embryos with the defect that would have been discarded.

A year ago we wrote about an Israeli team that also created a fragile X disease model using stem cells from PGD embryos. But the current team took this further by both finding the “how” in the cause, and testing an existing drug that seems to prevent the RNA from causing the gene to be turned off. The team’s work was written about on Yahoo Health.

Turning cancer cells into fat cells. For most people the only cell in their body more hated than a fat cell is a cancer cell. Now, a Japanese team suggests we might be able to get rid of those cancer cells by turning them into fat cells. Their work involves a fascinating process. They manipulate an often-overlooked part of the cell, the cytoskeleton, the fibers that help it hold its shape. In work published February 26 in Nature Communications they showed they could change stem cells into fat by changing their shape. They used a protein to disassemble the skeleton in mouse stem cells and reconfigured the fibers into the shape they would have in a fat cell, which is like a crescent. The cells then matured into fat. Since stem cells and cancer cells share some properties, the team speculated that it may be possible to turn cancer into fat in this article in the Japanese publication The Asahi Shimbun, which is in English.

Stem cells yield back pain relief—at least short term. A team from Emory in Atlanta reports that in a 100-patient international clinical trial a single injection of stem cells from bone marrow reduced back pain for at least 12 months. The researchers reported that, on average, the pain was reduced greater than 50 percent. They were using the type of bone marrow stem cell called mesenchymal stem cells and said they could see evidence of restored disc structure in degenerative disc disease.

The study does require some caveats. Some research shows that this type of stem cell may not produce bone and cartilage that is hard enough to withstand the long-term pressure that occurs in our joints and backs. But this was a relatively large study and with longer observation of the patients it might start to shed light on that issue. HealthCanal picked up the university’s press release. And CIRM has several projects using stem cells to try to correct bone and cartilage disorders.

Interview with a leading Parkinson’s researcher. For folks following efforts to grow dopamine-producing nerve cells from stem cells this interview provides a nice review of the progress and the hurdles that still need to be crossed. The discussion is with Malin Parmar of Lund University in Sweden about the NeroStemCell project which was funded by the European Union and completed its initial phase last May. She describes their success in generating replacement cells for the dopamine-producing nerves lost in Parkinson’s and getting those cells to restore function in mice. But she also details the many remaining steps, particularly producing the cells in sterile conditions that could be used in humans, and scaling up the production of cells to a quantity that could be a meaningful therapy. First published on a European web site devoted to innovation,, the interview was picked up by PhysOrg here.

Last year CIRM convened an international group of experts to discuss the status of using stem cells for Parkinson’s and the report from that workshop is available here.

Don Gibbons

Why a famous comedian told Congress that Alzheimer’s is no laughing matter

Over the years we have become used to seeing Hollywood celebrities testifying before Congress, championing a cause dear to their heart. Regardless of what we think of the individual involved, it’s a powerful and effective way to focus attention, particularly the media’s attention, on important issues.

Yesterday, comedian, movie star, writer, director and producer Seth Rogen appeared before a Senate Subcommittee and talked about his mother-in-law’s struggles with Alzheimer’s and the need for more funding for research into this awful disease.

So why am I writing about that here? Because Rogen is married to Lauren Miller, the Patient Advocate member of our governing Board for Alzheimer’s. It’s her mother he talks about when he says:

“After forgetting who her loved ones are, my mother-in-law, a teacher for 35 years, then forgot how to speak, feed herself, dress herself, and go to the bathroom by herself. All by age of 60.

“The situation is so dire, that it caused me, a lazy, self-involved, generally self-medicated man-child, to start an entire charity organization.”

The organization he founded with Lauren is called Hilarity for Charity and its goal is to raise money for research and for families struggling with the illness, and to raise awareness about the disease, particularly among younger people.

In his address to the Senators, Rogen uses humor to get their attention, but once he has that he talks movingly and with great passion. It’s a wonderful, powerful presentation that gets to the very heart of how this disease impacts individuals and families and why we need more money for research. So share this short video clip with your friends.

Right now there is no cure for Alzheimer’s, and the few therapies that do exist work for only about half the patients, and only help ease symptoms for between 6-12 months. That’s why we are funding 16 different research projects into finding new treatments for Alzheimer’s

kevin mccormack

Team tricked scar tissue on spinal cord injury into becoming new nerves without stem cell transplant

Here nerves (red) grow out of neural stem cells, but the current work coaxed other adult brain cells to directly become functioning nerves.

Many believe the ultimate solution in regenerative medicine will be inducing the body to mimic the activity of stem cells without having to transplant any cells. Now, a team at the University of Texas Southwestern Medical Center has used a two step process to turn the scar that forms at the site of spinal cord injury into functioning nerve cells.

They used a process similar to one they used in an earlier project published last September where they reported creating neural networks in the brains of mice. In both cases the researchers reprogrammed the nerve support cells known as astrocytes into functional nerves. Astrocytes tend to be abundant, particularly at the site of injury where they proliferate and form scar tissue that actually prevents regrowth of the damaged nerves.

The Texas team’s first step involved using a biologic substance to manipulate the expression of genes in the astrocytes at the site of spinal injury in the mice. They tried 12 different ones before they found one that is efficient in turning the protective cells into progenitor cells for nerves; think of them as middlemen between nerve stem cells and adult nerve. They then used a common drug called valproic acid to encourage those progenitor cells to mature into functioning nerves.

The work seems to map out a strategy to get new nerve growth directly in patients, or in vivo. The paper was published in Nature Communication and a press release from the university was picked up by ScienceCodex and it quoted the senior researcher Chun-Li Zhang on the impact:

Our results indicate that the astrocytes may be ideal targets for in vivo reprogramming.

However, given the amount of nerve damage that occurs in the elderly, either due to stroke and various degenerative diseases, the study also carries a strong caveat. While they were able to get the nerve reprogramming to happen in both young adult mice and in older mice, it was much less efficient in the older critters. Even in the younger adults it took four weeks to create the progenitor cells and another four weeks to get mature nerves. So the team indicated their next goal is improving the efficiency in both young and older animals.

You can read about some of CIRM’s dozens of projects trying to repair or regrow nerve cells in our stem cells and stroke fact sheet.

Don Gibbons

Dress Codes for Martians: how the Theater of Science can give us glimpses into the future

On Monday evening Friends of the Berkeley Lab hosted Science at the Theater. This ongoing series is a great example of how complex scientific topics can be made accessible to the public, and how the public will turn out to hear about them. Another example is CIRM’s grantee elevator pitch competition.

During the Monday event five LBL researchers gave short pitches describing why their research will lead to the “next big thing” . After all the pitches were completed the audience and a panel of judges voted for their favorite.

My personal favorite was by the chemist Guoying Chen. Her pitch was titled Making Better Batteries. She described how her research is designed to prevent lithium batteries from overcharging. Given recent problems such batteries have caused in airplanes and automobiles, I found her work very contemporary and compelling.

My son’s and the audiences’ overall favorite was a talk titled, Dress Code for Martians. In this extremely clever presentation, physicist Alex Zettl described research developing boron nitride fibers. He described how boron nitride is stronger and more resilient than existing materials. He also suggested boron based materials would make excellent scaffolding for cells, thus, there may be stem cell applications for his research. His punch line was, if we want to get to Mars, we will need the kinds of advanced materials his group is developing.

Two of the judges differed from the audience and voted Gloria Oliver’s Molecular Velcro as their favorite. Dr. Oliver described her work to create a new protein-like material that resembles tiny sheets of Velcro, each just one-hundred nanometers across (a nanometer is one billionth of a meter so this is unbelievably small). This “molecular Velcro” mimics the way natural antibodies recognize viruses and toxins, and could lead to a new class of biosensors. She imagined Molecular Velcro being integrated into environmental sensors.

One judge voted for Dr. Sylvian Costes who presented Tracking and Hacking Personal DNA Damage. Dr. Costes described his technology that allows individuals to monitor damage to their DNA and to assess their DNA repair capacities for the purposes of personalized and preventive health care. The technology is publicly available through Exogen Biotechnology.

I was actually intrigued by the idea of combining the Molecular Velcro and the DNA Tracking. Conceivably, these technologies combined, particularly if used on the population level, could be used to correlate exposure to environmental agents to impacts on DNA and or other biological markers. As technologies become cheaper, more portable and more accurate, the possibility for more precise measurement of the relationship between the environment and health becomes increasingly possible.

After the presentations, there was a question and answer session. Besides the Velcro and DNA tracking technologies, Dr. Steven Lanzisera described an approach for monitoring buildings to improve energy efficiency. One person in the audience asked the scientists whether they saw ethics and privacy concerns from these range of monitoring technologies. Lanzisera gave a very thoughtful response letting the audience know data about energy use are “not shared” out of concerns for privacy. [The question and response are at time stamp 1:31:58

The issue of privacy comes up frequently in biomedical and stem cell research. As reflected in the question Monday night, concerns typically center on protecting the privacy or identity of the person whose cells, DNA or even building you are looking at – the individual(s) that are subject to the research or monitoring.

However, as early adapters are embracing technologies, like those offered by Exogen, another group comes to mind – individuals who would rather not know. Personally, I find the idea of environmental and voluntary personal sensing appealing with a variety of up-sides for health and personal awareness. In fact, I have consented in the past to have environmental monitors placed in my home. At the individual level participation may not be risk free, perhaps someone could use my DNA for some nefarious act, but the risk seems minimal compared to everyday activities such as using a credit card on the Internet. As more and more people participate in biological monitoring, genetic testing and environmental sensing activities, we will learn more about the relationships between people and places. In some instances, as Dr. Costes noted, this knowledge may enable modifications in diet or other behaviors that could enhance health.

However, as another LBL study tells us a large fraction of particulate pollution in California comes from Chinese coal burning power plants. What if we learn that this particulate pollution is having a measurable health effect and there is nothing one can do about it? The literature on risk and society suggests that some individuals would find such knowledge stressful and disempowering. Thus information considered beneficial to those generating it may have the opposite impact on some.

Personally, I remain a technological optimist and believe there is an overall benefit to society from greater knowledge about health and the environment. However as we celebrate these technologies and imagine their future, we should be cognizant of possible downsides (as Lanzisera pointed out) and think creatively about how we may avoid them.

Geoff Lomax

The fight is on: predicting cancer outcomes with stem cells for better treatment choices

bone marrow with acute myeloid leukemia
(credit: Vashi Donsk; Wikimedia Commons)

“So doc, what’s my prognosis?”

It’s the question foremost on the minds of people who have been diagnosed with cancer. Yet giving a specific answer to an individual patient can be a challenge for cancer doctors. As the National Cancer Institute states on their website:

Because survival statistics are based on large groups of people, they cannot be used to predict exactly what will happen to an individual patient. No two patients are entirely alike, and their treatment and responses to treatment can vary greatly.

In recent years with the emergence of personalized medicine, the analysis of genetic mutations in the cancer cells of individual patients has helped more clearly define disease categories. Now, rather than inspecting mutations, a New York research team reports this month in the Journal of Clinical Investigation that comparing the pattern of chemical tags on DNA within healthy blood stem cells vs. cancerous cells can robustly predict how well an individual with acute myeloid leukemia (AML) may respond to chemotherapy.

As co-senior author Ulrich Steidl, MD, PhD, said in an Oncology Nurse Advisor article,

AML is a disease in which fewer than 30% of patients are cured. Ideally, we would like to increase that cure rate. But in the meantime, it would help if we could identify who won’t benefit from standard treatment, so we can spare them the debilitating effects of chemotherapy and get them into clinical trials for experimental therapies that might be more effective.

In a healthy individual, changes in the pattern of chemical tagging of the blood stem cells’ DNA – a process called methylation – plays a key role in determining which stem cells are transformed into mature cells of the blood system. In AML, the methylation pattern is disturbed and fewer stem cells fully mature into the various blood cells. Instead the blood stem cells make too many pre-white blood cells that are useless for fighting infection and in process crowd out critical red blood cells and platelets.

Steidl’s team analyzed the methylation pattern in the cancerous white bloods cells of nearly 700 AML patients as well as in blood stem cells of a handful of healthy people. They were able to develop a scoring method that showed those AML patients whose cancer cells had a methylation signature that more closely resembled the signatures of healthy blood stem cells, were predicted to live longer. Steidl concluded that their methylation signature test “was clearly superior to similar tests that have been used. “

Although the stem cells studied in this report won’t lead directly to new treatments, they provide a path to more specific answers that are so critical to people and their loved ones who face scary choices in their fight against cancer.

For information about CIRM-funding of stem cell-based leukemia projects, visit our leukemia fact sheet.

Todd Dubnicoff

Actor, writer and science-buff Alan Alda’s call to action for scientists

Alan Alda

Who knew that movie star, actor and writer Alan Alda and I had so much in common! Well, one thing in common at least – an appreciation of the importance of scientists also being good communicators.

Alda is best known for his role as Hawkeye Pierce in the TV series “M*A*S*H” but he’s also a huge fan of science and was the host of the PBS TV series “Scientific American Frontiers”. He is now the founder of the Alan Alda Center for Communicating Science at Stony Brook University.

In an interview in the New York Times Alda talks at length about his fascination with science and his desire to solve one of the biggest problems the scientific community faces, namely the challenge of communicating with the rest of us:

 “scientists often don’t speak to the rest of us the way they would if we were standing there full of curiosity. They sometimes spray information at us without making that contact that I think is crucial. If a scientist doesn’t have someone next to them, drawing them out, they can easily go into lecture mode. There can be a lot of insider’s jargon.

If they can’t make clear what their work involves, the public will resist advances. They won’t fund science. How are scientists going to get money from policy makers if our leaders and legislators can’t understand what they do?” 

It’s an important point, and one we try to make when we work with the researchers we fund: this is taxpayer money that is helping them do the work they love, but for the public to continue to support this work they need to know what it is and how it affects them.

Last year we held our ‘CIRM Grantee Elevator Pitch Challenge’ where we asked researchers to videotape an Elevator Pitch, where they explained their work and why it’s important to the public in around 30 seconds. Some researchers did a good job, some did a great job, and some were, well, works in progress.

The point we were trying to make to them, is the point Alan Alda does such a great job of articulating in this New York Times interview, that science matters to all of us, it shapes the world around us today, and it’s shaping the world we’ll face tomorrow. And it’s exciting stuff. And the better job they do of sharing that excitement with the rest of us, the more likely the public will support the research.

“Every experiment is a great story. Every scientist’s life is a heroic story. There’s an attempt to achieve something of value, there’s the thrill of knowing the unknown against obstacles, and the ultimate outcome is a great payoff — if it can be achieved. Now, this is drama!”

kevin mccormack

Turning skin into mature liver cells. And they work!

skin cells labeled with fluorescence dyes

It’s one thing to get a stem cell to turn into something that closely resembles another kind of cell, say a heart cell. But it’s another thing altogether to get it to change into a cell that not only resembles another cell, but acts exactly like it too. That’s what CIRM-funded researchers at the Gladstone Institutes have done with liver cells.

It’s a tricky process, but an essential one if you want to develop new therapies. Previous attempts with liver had come close, but none of the cells were able to survive and function after being transplanted into existing liver tissue. So the researchers at Gladstone, led by Sheng Ding, Ph.D., developed a new multi-step process to change ordinary skin cells into fully mature, adult liver cells.

Their findings are published in the latest issue of the journal Nature

Step One: Instead of taking a skin cell and, by manipulating a series of genes, turning it all the way back to an embryonic-like state, they reprogrammed the skin cell and transformed it into endoderm – a cell type that helps makes up many of our organs, including the liver.

Step Two: Using a set of genes and compounds they were able to change these endoderm cells into functioning liver cells.

Step Three: They transplanted these newly created liver cells into mice and over the next nine months were able to measure increased levels of human liver proteins in the mice, a clear sign the transplanted cells had become mature liver cells and were working.

In a news release  another CIRM-funded researcher Holger Willenbring, M.D., Ph.D., an Associate Professor at the University of California San Francisco, and one of the senior author’s of the paper, talked about the potential significance of their findings:

“Many questions remain, but the fact that these cells can fully mature and grow for months post-transplantation is extremely promising. In the future, our technique could serve as an alternative for liver-failure patients who don’t require full-organ replacement, or who don’t have access to a transplant due to limited donor organ availability.” 

According to the American Liver Foundation there are around 17,000 Americans waiting for a liver transplant. Every year around 1,500 people die waiting for a donated liver to become available.

Dr. Willenbring is also featured in a CIRM Spotlight on Liver Disease.

kevin mccormack

Stem cell stories that caught our eye: tissue engineering bone, cartilage for arthritis and partisanship 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.

TED video on engineering new bone. Two young Columbia University bioengineers use this TED video to remind us how barbaric our current system of obtaining spare parts for humans can be, and how revolutionary it will be to grow new ones from cells. It reminded me of going to the junkyard with my dad as a kid looking for a wrecked car that was a similar to the old family Chevy to find a part. Currently patients needing a replacement piece of bone must either accept bone from a cadaver or let a surgeon chip off a piece of bone from their hip or other spot in their body.

The New York duo does a nice job of explaining their work starting with a CT scan to get the exact dimensions of the patient’s defect. They then mold the exact same shape from animal bone that has had all its whole cells removed so that what remains is a scaffold. They describe seeding that with stem cells from the patient’s own fat tissue and then growing it in a bioreactor that they cleverly describe as a fancy fish tank. But they spend a bit of time in the 4.22-minute video explaining the nuance of getting just the right mix of nutrients in that fish tank.

One of the researchers gave a nice quote about the hope for their work: “I would love to see congenital defects be a statistic from the past.” That was the goal of many of the researchers who presented at a CIRM workshop of tissue engineering described in a report on our web site.

Genes plus stem cells for aching joints. Researcher pretty routinely direct stem cells in the lab to become specific types of tissue, but too often loose control of the cells’ fate after they are transplanted into a body. Duke University researchers think they have found a way to keep the cells from changing their minds after transplantation—in this case for growing new cartilage for damaged joints. Like many other groups they use a synthetic scaffold to get more control of the shape of the final tissue, but they enlist genetic engineering in order to keep the stem cells they seed on the scaffold heading toward the desired form of cartilage. They embed the scaffold with a virus carrying the gene for the growth factor used to direct stem cells toward cartilage in the lab. This virus has been used safely in other forms of gene therapy.

The researchers published their work in the Proceedings of the National Academy of Sciences and Genetic Engineering & Biotechnology News wrote about the work. CIRM projects for arthritis can be found on our web site.

Disease-specific embryonic stem cell lines. Some of the most important stem cell research today uses cells containing genes that cause certain diseases. Most often, researcher create those stem cells by reprogramming skin or other tissue from patients with the disease to create iPS type stem cells. But you can also get those disease-specific cells through creation of embryonic stem cells from embryos donated by couples that have at least one person carrying the defective gene. Such couples often choose to conceive a child through in-vitro fertilization (IVF). This allows them to add the step called pre-implantation genetic diagnosis (PGD), which lets them test each embryo created to see which ones carry the genetic defect. They then implant the normal embryos hoping for a healthy baby, and can donate the ones carrying the disease gene to research.

An Australian company recently made 43 such stem cell lines, representing 24 genetic diseases available to researchers around the world through the registry maintained by the National Institutes of Health (NIH). The Australian publication LifeScientist wrote about the project. These cells will have great value in letting us compare disease-specific cell lines made through iPS and those made from embryos. We know the two types of stem cells have subtle genetic differences, but this type of comparison will let us better determine if the differences are relevant to disease modeling. This work highlights the need for independent funding sources like CIRM. The NIH remains barred from funding the creation of any new stem cell lines by the Dickey amendment to its federal authorization.

Call for less partisanship in science debates. The blogging web site science 2.0 used a scholarly publication Tuesday to remind us that science data are selectively used and ignored by partisans on the right and the left. The authors’ starting point was a publication in the journal PLOS by American University professor Matthew Nisbet. In the paper, Nisbet divides the public into four groups: scientific optimists, scientific pessimists, conflicted and disengaged. He finds that placement in one group or another often is more dependent on education and economic attainment than partisan position. He suggests that those of us who care about a society driven by well-interpreted scientific data should start our public communication by addressing people’s beliefs about science and its role in society.

The science 2.0 writers use an example from the stem cell field. They remind readers that President Push did not ban embryonic stem cell research as many on the left like to say. He allowed the first ever federal funding of the work, but at such a small narrow trickle, that he severely hindered advancement of the field. (That last sentence is my interpretation, not the science 2.0 writers.)

Don Gibbons

It’s a big breakthrough. Wait, maybe, maybe not. Taking a second look at STAP

It’s always fascinating watching the arc of a news story. I woke up on January 29th to news, as the BBC World Service put it, “of a big breakthrough in stem cell research.” The reporter then went on to explain how scientists had created a whole new type of pluripotent stem cell – the kind that can change into any other kind of cell – by simply “shocking” a normal cell by immersing it in acid or subjecting it to other kinds of stress.

News outlets around the globe quickly picked up the story and ran their own versions of it. For days the media was positively giddy with stories about this new discovery – called stimulus-triggered acquisition of pluripotency (STAP) cells – with lots of speculation about how this could change the science and possibly even eliminate the need for embryonic stem cells.

We blogged about it February 3, but with the word “caveats” in the headline and the bulk of the post devoted to debunking the hype in the news coverage and discussing the need for further validation from the scientific community.

In the last week the tide has certainly turned. A growing number of news outlets, journals and blogs have taken a step back and begun to question not just some of the claims about STAP cells, but whether these cells even exist.

The original study – by Haruko Obokata of the RIKEN Center for Developmental Biology (CDB) in Kobe, Japan, and researchers at Harvard Medical School in Boston – was published in the journal Nature But just a week later anonymous bloggers at the PubPeer website raised questions about certain images used in the manuscript, suggesting they might have been altered.

Over the next week or so other scientists joined in expressing their doubts. U.C. Davis stem cell scientist and avid blogger Dr. Paul Knoepfler (we fund some of his work) has written extensively on this topic and quoted a piece from a writer with Nature, the publication that printed the original story, who reported that other scientists who had tried to replicate the work failed, saying:

“None of ten prominent stem-cell scientists who responded to a questionnaire from Nature has had success.”

Knoepfler has charted the growing uncertainty about STAP cells by doing a weekly poll among his readers (a very scientifically literate group) about whether they believe these cells are real. In week 1 there was a clear inclination among those who voted in favor of them being real. By week 2 that had changed with the numbers who believed in them equally divided, and a growing number of people on the fence.

The news that other scientists haven’t been able to replicate the experiments has now led the Riken Institute in Japan, where the lead researcher in the study works, to carry out its own investigation.

And so now the news is all about the doubts and uncertainty. How quickly the news coverage has changed, racing from celebration to consternation. And yet just because this is the latest swing in the STAP story it doesn’t mean that the research won’t turn out to be valid, or that the findings won’t ultimately prove to be enormously important.

Science rarely progresses in a simple, straight direction. Things that we thought were breakthroughs sometimes turn out to be wrong turns. Things we thought of minor importance sometimes turn out to be very important indeed. We can only find out which is which by constant examination of the data, by doing new experiments and by keeping an open mind.

What this series of stories shows is not that these scientists made a big mistake – we don’t know that. It just reminds us we all need to be very careful about leaping to assumptions about any potential breakthrough.

To quote the old Russian proverb – so beloved by President Reagan – Доверяй, но проверяй (doveryai, no proveryai). Which means Trust, but Verify.

 kevin mccormack

Be still my beating ventricle – Researchers come up with a better way to make heart cells

  iPS heart cells beating in a dish: Courtesy Wired magazine

Each new breakthrough in stem cell science is cause for celebration. But pretty quickly after the champagne corks have flown researchers start asking follow-up questions such as “how can we do this faster, more efficiently, more effectively?”

For some years now researchers have been able to take stem cells and turn them into heart muscle cells that actually beat in time with each other. Now CIRM-funded researchers at the Gladstone Institutes have come up with a way to create those same kinds of cells in a more efficient and, importantly, more complete way.

Sheng Ding, Ph.D., and his colleagues describe their methods and findings in the latest issue of Cell Reports.

With previous methods scientists had to insert several genetic factors to change or reprogram a skin cell into a beating heart cell. That was complicated, time consuming and potentially dangerous since the insertions could lead to tumor growth. But Dr. Ding and his team took another approach. They took skin cells from adult mice and used those to look for chemical elements, compounds called “small molecules”, that could do the same job.

After much detective work they whittled down the list of possible candidates to a combination of four molecules, which they called SPCF, and showed this could turn ordinary skin cells into beating heart cells. But they weren’t finished yet because the cells didn’t beat quite the same as mature adult heart cells would. So they added one more ingredient, a genetic factor called Oct4, and that did the trick.

In a news release about the research Dr. Ding says:

“Once we added Oct4 to the mix we observed clusters of contracting cells after a period of just 20 days. Remarkably, additional analysis revealed that these cells showed the same patterns of gene activation and electric signaling patterns normally seen in the ventricles of the heart.”

This discovery gives researchers another option, a pharmaceutical-based one rather than a genetic-based one, as they try to find the best ways to regrow heart muscle damaged by disease or a heart attack.

In the search for new treatments for deadly diseases, it’s always good to have as many options as possible, because the more shots on goal you take the more likely you are to score.

kevin mccormack