A call for scientists to speak out for Stem Cell Awareness Day

SCAD campaign

The International Society for Stem Cell Research (ISSCR) and the journal Cell Stem Cell, are asking stem cell scientists to take part in a social media campaign with the hashtag #AStemCellScientistBecause between October 1 and October 14.

“We want to share with the world our pride and excitement to be a part of a worldwide effort to transform human health,” the association states on a web page created for the event, calling the effort a “campaign to give a voice to the scientists behind the research.”

ISSCR suggests several ways to take part:

  • Tweet a brief statement about why you entered the field,
  • Record a 10-20 second video to accompany the Tweet,
  • Talk to peers about taking part,
  • Share and retweet favorites posts.

The journal’s October issue will include an article with contributions from all the first authors of papers in the issue stating why they entered the field as well as contributions from other authors in the issue.

As always, CIRM is facilitating getting researchers we fund into high school classrooms on October 14th to give guest lectures. We expect to reach more than 50 classrooms including several school-wide assemblies this year.

Several institutions in California will be hosting special events to commemorate Stem Cell Day this month. And if you are across the border, the MaRS center in Toronto is hosting the children’s museum exhibit we helped develop, “Super Cells: The Power of Stem Cells.”

All the events con be found at http://www.stemcellday.com/

Stem cell stories that caught our eye: better heart muscle, first patient with eye cell patch, brain cross talk and gut bugs

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.

Growing better heart muscle in the lab. While researchers have been able to grow beating heart cells from stem cells in a dish for many years, those beating blobs of cells have not looked or acted much like the long strong muscle fibers found in a normal heart. A team at Stanford, with collaborators at the Gladstone Institutes have spent much of the past five years looking for ways to make lab-grown heart muscle more like the real thing.

Heart muscle matured from stem cells functions better when grown in long, thin shapes.

Heart muscle matured from stem cells functions better when grown in long, thin shapes.

They published a couple of solutions in the Proceedings of the National Academy of Sciences this week. One of the keys was to make the stem cells feel more like they are in their natural environment, which is full of physical tension. When they grew the stem cells on substrates that provided that type of tension they got stronger heart muscle better able to beat in a synchronized rhythm. They also found that stem cells grown in long, narrow chambers produced heart muscle closer in appearance and function to the narrow muscle fibers found in normal hearts.

The press release, written by our former colleague Amy Adams who now works for the University, was picked up by Medical Express.

First patient in trial for blindness. Doctors at the Moorfields Eye Hospital in London have used specialized eye cells derived from embryonic stem cells and grown on a synthetic scaffold to try to reverse blindness caused by age-related macular degeneration(AMD). Prior clinical trials have injected similar cells but without the supporting structure of the patch to hold them in place.

Also, prior trials have aimed to halt the progressive loss of vision in the dry form of macular degeneration. This trial is trying to reverse damage already done by the wet form of AMD. Each of the groups use embryonic stem cells and first mature the cells into a type of cell found in the back of the eye’s retina, retinal pigmented epithelium (RPE) cells.

“The reason we are very excited is that we have been able to create these very specific cells and we have been able to transfer them to the patient,” lead researcher Lyndon Da Cruz told a writer for the Huffington Post. “It’s the combination of being able to create the cells that are missing and demonstrate that we can safely transplant them.”

CIRM funds a team at the University of Southern California and the University of California, Santa Barbara that has collaborated with the London team and plans to use a similar patch system on a trial set to begin in the next few weeks.

The London news got broad pick up in the media, including this BBC Video.

Cross-talk in the brain linked to success. The National Institutes of Health issued a press release this week describing two early results of its major Brain Initiative. One team from the University of California, San Francisco, provided an explanation about why primate brains are so much bigger than other mammals, and a team from Oxford and Washington University in St. Louis mapped cross talk between different parts of the brain to various personality traits.

The second group collected data on 280 measures such as IQ, language performance, rule-breaking behavior and anger that they mined from the initiative’s Connectome Project. Their analysis of 461 people found a strong correlation to sections of the brain talking to each other when in a resting state and positive personality and demographic traits. Those included high performance on memory tests, life satisfaction, years of education and income.

The UCSF team showed that brain stem cells during early development produce as much as 1,000-fold more neurons in primates than in lower mammals. More important, they isolated a reason for this strong performance. As the brain gets bigger the stem cells don’t have to continually migrate greater distance from their homes, called the stem cell niche. Instead they seem to pack their bags and take the niche with them.

“It is great to see data from large investments like the Human Connectome Project and the BRAIN Initiative result in such interesting science so quickly,” said Greg Farber of the National Institute of Mental Health in the release.

Have to agree.

The interplay of bugs and genes in our gut. The consumer press spends a considerable amount of time talking about the bacteria in our digestive tract, and now a team a Baylor College of Medicine in Houston has produced some data that suggests these microbial cohabitants of our bodies, called the microbiome, become important early in our development.

In research published in the journal Genome Biology and in a press release picked up by Medical Express, the researchers showed that the microbiome in mice during the period they are nursing helps determine which genes are turned on or turned off, and those settings, called epigenetics, follow the mice through their adult life. Specifically, they found that the gut microbiome impacted the function of gut stem cells that we rely on to replace the lining of our digestive system approximately every four days.

“This promises some exciting opportunities to understand how we might be able to tailor one’s microbiome exposure during infancy to maximize health and reduce gastrointestinal disease throughout life,” said one member of the team, Robert Waterland.

Three teams empower patients’ immune systems to oust cancer

Immuno-oncology is all the rage now in biotech publications, with due cause. It is producing some pretty impressive results in patients who failed other therapies. Most of what gets written about involves strengthening or unlocking the action of one immune cell, the T cell. But our immune systems are armed with many types of ammunition; we have multiple kinds of cells that can initiate or follow through in getting rid of unwanted invaders or cancers. CIRM funds three clinical trials that test these lesser-traveled routes to juicing up our immune response to cancer.

Robert Dillman has worked to bring immune therapy to cancer patients for 25 years.

Robert Dillman has worked to bring immune therapy to cancer patients for 25 years.

While this field is hot now, it is not new. It has been elusive; researchers have tried for decades to harness our multi-talented immune system in the war on cancer. One of those researchers, Robert Dillman, who has been working on it for 25 years, now leads a CIRM-funded clinical trial in Phase 3, which is the last leg in a long journey to having a therapy approved for any patient with metastatic melanoma.

Another CIRM-funded team is also in a Phase 3 trial, in this case a therapy for the brain cancer glioblastoma developed by ImmunoCellular Therapeutics. The third CIRM-funded team at Stanford is in the middle of an early phase trial testing for safety and early signs of effectiveness with a therapy that could become an off-the-shelf therapy for many different cancers.

25-year effort getting results

Dillman now works for Caladrius Biosciences, the company conducting the Phase 3 trial in many medical centers around the U.S. He heads the clinical trial team funded by CIRM to conduct the California portion of the trial. But he has been working on the concept behind the therapy since the 1990s, most of the time at Hoag Hospital in Orange County. His mom was diagnosed with cancer when he was 14, and she died of the disease when he was an undergraduate at Stanford. His entire career has been focused on immuno-oncology.

The current effort uses a part of the immune system called dendritic cells that are derived from the patient’s blood. A patient’s tumor cells from a cell line and their dendritic cells are exposed to each other in a lab culture flask. What dendritic cells are really good at is gobbling up the cancer cells, then presenting pieces of the destroyed cancer cells to the immune cells responsible for getting rid of tumors. So, when given back to the patient the dendritic cells present the cancer bits, or antigens, like road maps to the immune cells that can then seek out and kill the cancer stem cells. The company produced a great video explaining the process.

Unlike most of the other immunotherapies that generally only present or target one CSC antigen, the Caladrius strategy presents a multitude of CSC antigens through the dendritic cells. The therapy has been associated with minimal side effects and theoretically should be more effective than other therapeutic cancer vaccine approaches. With so many specific targets, the cells are less likely to cause immune attack on healthy cells and more likely to find all the renegade tumor cells. This therapy is also a bit slower acting, which is actually a good thing. Many of the other immune therapies trigger such a strong immune response, they cause flu like symptoms that sometimes require the therapy to be halted. The dendritic cell therapy has few side effects reported so far.

Caladrius plans to conduct the trial at 32 locations, with 20 of them recruiting patients currently. The first patient was dosed in June, and a total of 250

Norm Beegun was treated in an earlier phase of the Caladrius trial.

Norm Beegun was treated in an earlier phase of the Caladrius trial.

patients will be randomly selected to get the therapy or not, with two thirds getting the therapy. The researchers plan to review the interim results as early as the end of 2017.

One patient from the earlier phase trials of the therapy, Norm Beegun, believes he definitely benefited from the treatment and told his story to our board in May.

Other approaches to ousting cancer

The CIRM-funded team at Stanford began an early phase trial in August 2014 using an antibody that blocks a receptor on the surface of CSCs called CD47. One of the researchers on the team, Irving Weissman, has dubbed that gene the “don’t eat me gene(video)” because it tells the immune system cells responsible for getting rid of tumors to not do their job. When CD47 is blocked, the immune system cells called macrophages are able to destroy—in essence eat—the CSCs.

The initial study primarily seeks to determine safety and the best dose for moving forward. It is enrolling patients with advanced-stage solid tumors. So far 12 patients have been treated with five different doses, and the team continues to screen patients for higher doses to be treated in the coming months. The trial is open only at Stanford Cancer Center under the leadership of Branimir Sikic.

The team at ImmunoCellular plans to enroll 400 brain cancer patients at 120 clinical trial sites around the U.S., Canada and Europe. They are also developing a way to turn a patient’s dendritic cells into a vaccine that helps the immune system target cancer stem cells.

CIRM Fights Cancer: Two teams develop therapies to stop and eliminate cancer stem cells

Six out of the ten best selling drugs are proteins called monoclonal antibodies. But the prospect for monoclonal antibodies was not always so bright. It took a decade after their discovery in 1975 before they found any clinical use, even then it was very limited use for organ transplant rejection. It was a full twenty years before their first wide spread use in cancer. One of the first cancer therapies using antibodies, Herceptin approved in 1998, keeps many breast cancer patients alive today.

UCLA's Dennis Slamon

UCLA’s Dennis Slamon

Dennis Slamon, worked for more than a decade in his lab at the University of California, Los Angeles, to get Herceptin tested, approved and marketed by Genentech. That story, told in “The Emperor of All Maladies,” shows him working against skeptics and critics often with scant financial support. Now, he has turned that laser focus on finding a therapy that can seek out and destroy cancer stem cells from a broad array of cancers—an effort he began in earnest some five years ago with an early disease team grant from CIRM.

That early CIRM grant let his team test several different compounds alone and in combination with standard therapies to settle upon one drug that targets a protein called PLK-4, a specific kinase that is found in many cancer stem cells. CIRM now funds an early phase clinical trial testing that drug in several different solid tumors. The University Health Network in Toronto, partnered with CIRM in supporting the early work, and now also funds another clinic site for the same trial at the Princess Margaret Hospital in Toronto.

All doses safe so far

So far, seven groups of patients made up of three patients each, have been given increasing doses of the drug. The Slamon team suspected that the early doses administered in the trial were likely to be too small to be effective but the Food and Drug Administration appropriately insists on the demonstration of safety first for new

Trial Patient Frank Gonzalez tells his story in his own words

Trial Patient Frank Gonzalez tells his story in his own words

therapies. So far in the study none of the groups have shown any toxicity and Slamon thinks, based on the animal data that they are now near a dose where they could see patient tumors responses. Since each group has to be monitored for four weeks before the next group can be treated it has been nearly a year since the trial began, but Herceptin showed Slamon has the stamina to stick with a therapy that makes sense.

One of the early participants in the trial, Frank Gonzalez, knew he would probably be getting a dose too low to be effective, but felt it was valuable to participate for the potential long term outcomes of the therapy. (link to his story and video)

Second trial targets leukemia stem cells

CIRM funds a second clinical trial that targets a protein broadly found on cancer stem cells, with the current trial treating leukemia. This therapy, an antibody being tested at the University of California, San Diego, targets a protein called ROR1. When the antibody blocks that protein it prevents the cancer stem cells from proliferating and encourages them to die. We at CIRM are proud of the name the team gave the antibody, Cirmtuzumab. This trial, too, was required to start at a very low dose to guarantee safety and has slowly escalated the dose with the expectation of the trial continuing for another year. One of the lead researchers on that trial, Catriona Jamieson, also thinks they may be near a therapeutic dose where they may see tumor response.

Many companies have jumped into the field developing traditional drugs and antibodies targeting cancer stem cells. As always it is nice to have colleagues working on many different routes to the same goal. It makes sense that some of these should work. Patients fearful of their doctor telling them “it’s back” deserve nothing less.

Pioneering patients heroes of early clinical trials

When Frank Gonzales was diagnosed with colorectal cancer in November 2010 it was the start of a long fight against the disease.

Chemotherapy helped keep the cancer in check, but it wasn’t a cure. So when Frank heard about a new experimental treatment, that seeks out and destroys cancer stem cells, he was intrigued.

Frank talked to UCLA’s Dr. Zev Wainberg, who is running the clinical trial funded by CIRM: “I knew it was a study and everybody wasn’t getting the same dosage but after having gone through all the other treatments this was easy.”

Frank took a single pill every day, and says he experienced no side effects. After six months he had to drop out of the trial to receive radiation.

Frank’s cancer is now in remission and he’s been able to go back to work. He doesn’t know if the pills helped but he’s proud of being a stem cell pioneer and hopes the first-in-human therapy proves effective so that one day many others will be as lucky as he is.

“It is pretty amazing. I hope they close in on it. Figure this thing out, because there’s a lot of need for it.”

CIRM fights cancer: $56 million for 5 clinical trials to vanquish tumors for good

target on CSC[This is the first of three stories on CIRM’s Cancer Fight that we will post this week. Tomorrow’s will discuss two projects that attack cancer stem cells directly and Thursday’s will describe three projects that help our immune system wipe out the traitorous cells.]

It’s back—two words we would like to remove from the cancer caregivers’ vocabulary. Many researchers blame cancer stem cells for this too common occurrence, saying cancer stem cells have ways of avoiding most traditional therapies and trigger the tumor’s return. Others prefer the term “tumor initiating cells.” But whatever you call them they need to be dealt with if we are going to make major improvements in cancer patient survival.

Cancer_stem_cellsCIRM is investing $56 million in five clinical trials targeting cancer stem cells (CSCs), the most advanced projects in our over $200 million commitment so far, to fighting cancer. Two of these trials use agents that target the cancer stem cells directly and three use agents that enable a person’s immune system to do a better job of getting rid of the CSCs.

Trials that target cancer stem cells directly

 One of the clinical trials directly targeting CSCs uses a type of protein called an antibody to seek out the renegade stem cells and initiate their demise. Antibodies home to specific proteins on the surface of cells called antigens. Researchers have been able to identify a few antigens that seem to be almost exclusively on the surface of CSCs and they have become targets for therapy.

A team at the University of California, San Diego uses an antibody named after our agency Cirmtuzumab to fight chronic lymphocytic leukemia. It targets the protein ROR1 that is abundant on CSC in the leukemia but not on normal blood-forming stem cells. Once bound on the cells Cirmtuzumab seems to prevent them from proliferating and migrating to other parts of the body and promotes them to go through a form of cell death called apoptosis.

The second trial directly attacking CSCs, at the University of California, Los Angeles, targets various solid tumors. They use a drug that affects the CSCs ability to replicate. It binds to and inhibits a protein, called a kinase, that the CSCs use when they divide.

Trials that activate the immune system

 A third clinical trial, at Stanford, also uses an antibody, but in this case it blocks a protein the CSCs use to fend off the cells in our immune system that routinely destroy emergent cancers in all of us. Immuno-oncology, the process of juicing up our immune response to cancer, is one of the hottest areas in cancer research and on Wall Street right now. But most of those efforts target a part of the immune system called the T cell. The Stanford team mobilizes a different immune cell, the macrophage, which routinely gobbles up dying, damaged or cancerous cells.

One beautiful thing about all three of these therapies is they could reverse a decade-long trend of new cancer therapies being targeted to increasingly narrow populations of cancer patients, resulting in extremely high costs per patient. Because the proteins targeted by these therapies seem to be shared across a great many types of tumors, they could be broad-spectrum cancer strategies that could be delivered at a lower cost.

CIRM currently funds five clinical trials targeting cancer stem cells.

An additional five cancer clinical trials have been undertaken based on early research funded by CIRM.

The fourth CIRM-funded clinical trial also seeks to increase our natural immune response, in this case in notoriously hard to treat metastatic melanoma. Like the Stanford team, this project by researchers at the firm Caladrius Biosciences targets a type of cell different from most immuno-oncology. In this case they derive cells called dendritic cells from the patients’ blood and establish a cell line from their tumor. In the lab they mix the cell types together and the dendritic cells gobble up the tumor cells including the cancer’s antigens, those surface proteins that act as identification tags. When re-infused into the patient the dendritic cells do what they are really good at: presenting antigens to the immune cells responsible for getting rid of tumors. Dendritic cells display the antigens like road maps to the immune cells that can then seek out and kill the cancer stem cells.

The fifth CIRM-funded trial uses a similar concept activating a patient’s dendritic cells with antigens from their brain cancers, known as glioblastomas. That trial is being conducted by ImmunoCellular Therapeutics

The first three trials are all early phase studies looking to test safety and determine what is the best dose to use going forward. The last two trials are more advanced, so-called Phase 3 studies of a dose already having shown signs of benefit in earlier trials.

Stem cell stories that caught our eye: lab-grown kidneys that work, finding blood stem cells’ home and colitis

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.

Lab grown kidneys able to take a leak. While a few teams have been able to grow parts of kidneys in the lab using stem cells, they could never show full function because kidneys are not a closed system. They need connecting plumbing and a shutterstock_251360653bladder to collect fluid before urine can be expelled. Now, a team in Japan has built kidneys as well as those other parts in the lab. When they were implanted in rats and pigs and connected to the animals’ own plumbing the man-made organs successfully peed.

The BBC ran a story on the work that included a quote from noted stem cell expert Chris Mason of University College, London:

”This is an interesting step forward. The science looks strong and they have good data in animals. But that’s not to say this will work in humans. We are still years off that. It’s very much mechanistic. It moves us closer to understanding how the plumbing might work.”

The team published the research in the U.S. Proceedings of the National Academy of Sciences.

Seeing through bone to track stem cells. Yes we know blood-forming stem cells reside in bone marrow, but that is a pretty big base of operations. We really haven’t known where in the marrow they tend to hang out and in what sort of groupings. A team at Children’s Research Institute at the University of Texas Southwestern published research this week using new imaging techniques to map the home of all the blood stem cells in marrow and it showed some surprising results.

“The bone marrow and blood-forming stem cells are like a haystack with needles inside. Researchers in the past have been able to find a few stem cells, but they’ve only seen a small percentage of the stem cells that are there, so there has been some controversy about where exactly they’re located,” said UT’s Sean Morrison in a press release posted by Technology Networks.

“We developed a technique that allows us to digitally reconstruct the entire haystack and see all the needles – all the blood-forming stem cells that are present in the bone marrow – and to know exactly where they are and how far they are from every other cell type.”

They found the blood-forming stem cells clustered in the center of the bone marrow rather than near the edges of the bone as was presumed. This improved understanding of the stem cells’ natural environment should make it easier to replicate the cells behavior in the lab and, in turn, lead to improved stem cell therapies.

Help for colitis patients resistant to therapy. About two-thirds of patients with colitis and Crohn’s disease do not respond to one of the leading medications that blocks a protein considered key to the inflammatory process, Tumor Necrosis Factor (TNF). A CIRM-funded team at the Children’s Hospital Los Angeles published research this week suggesting why and offering possible new options for treatment.

“Understanding this mechanism allows us to target new therapeutic approaches for patients who don’t respond to current therapies,” said principal investigator Brent Polk in a university press release posted at Eurekalert.

The mechanism surprised his team. They found that TNF in these patients actually protected against inflammation by inhibiting one type of the immune system’s T cells. The interplay between TNF and those culprit T cells now becomes a target to therapeutic intervention.

Stem cell stories that caught our eye: our earliest days, cell therapy without the cells and unproven therapies

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.

2-cell embryoMapping our earliest days—as an embryo. We have some 23,000 genes in every cell of our body, but on day two after fertilization just 32 are switched on. A team at Sweden’s Karolinska Institute has for the first time mapped all the gene activity for the first few days of embryo development—information that is yielding clues for developing better fertility treatments.

One of their more interesting finding was that by day three, the number of active genes has grown to 129 even though the embryo has only grown from four to eight cells.

“These genes are the ‘ignition key’ that is needed to turn on human embryonic development. It is like dropping a stone into water and then watching the waves spread across the surface,” said the project leader Juha Kere in an article in Health News Digest.

As with much science today, the team took advantage of rapidly advancing technology in genetic analysis to map the gene activation.

Sending the message without the messenger. In many experimental stem cell therapies it’s not the stem cells themselves that are expected to make the repair but rather other cells in the body that respond to chemical messages released by the stem cells. Stem cells often send out those messages in packets called exosomes, which has led several teams to start using the exosomes alone for repair.

A stem cell releasing exosomes, sort of like little medicine bags.

A stem cell releasing exosomes, sort of like little medicine bags.

One group in Germany just published results in Stem Cells Translational Medicine suggesting that in at least one disease, a mouse model of stroke, exosomes trigger as much repair as whole stem cells. The researchers from the University of Duisburg-Essen claim to be the first to publish a side-by-side comparison of exosomes, which are also called extracellular vesicles (EVs) and whole stem cells.

“The fact that intravenous EV delivery alone was enough to protect the post-stroke brain and help it recover highlights the clinical potential of EVs in future stroke treatment,” said the two lead researchers in a press release distributed by the journal and picked up by BioSpace.

 They reported that the exosomes promoted brain recovery and protected the mice from post stroke inflammation that can cause ongoing damage.

Three hits on unproven stem cell therapy. Yesterday’s news feed brought in three welcomed pieces trying to explain why so many stem cell treatments being offered today are unproven, skirt regulations and may be a rip-off.  

 A group of neurologists from Ohio State University wrote a piece on the growing problem of “stem cell tourism” in the journal JAMA Neurology. The piece got picked up by many news outlets including Fox News. In particular, the authors noted internet advertisements suggesting stem cells are proven to help multiple sclerosis, ALS (Lou Gehrig’s disease) and other hard or impossible to treat neurological conditions. They called upon their fellow neurologists to do a better job of advising their patients on the issue.

“We must help educate our patients not only in the clinic setting, but also by working with patient advocacy groups such as the National Multiple Sclerosis Society and the ALS Association,” said one of the Ohio State authors, Jaime Imitola.

USA Today published a pair of pieces. One dealt with athletes making very visible trips to clinics offering unproven stem cell therapies and the power their fame has to attract other customers. The second piece discussed face creams that claim to have benefit due to stem cells and the lack of data and often lack of logic behind most of those claims.

stem cell drive through

From Paul Knoepfler’s Stem Cell Blog

Brent Schrotenboer wrote both pieces and he did the best job I’ ve seen in the consumer press of explaining how the US-based clinics skirt FDA regulation and fail to provide data showing their stem cells caused an improvement in the athletes beyond the other therapies they received at the same time. At almost 3,000 words the piece is unusually long for USA Today and at that length he has the opportunity to cover quite a bit of nuance between some of the various clinic offerings. He quotes a CIRM-grantee from the University of California, San Diego, Lawrence Goldstein a couple times, including in the concluding paragraph:

“It’s hard to write good law and regulation that allows legitimate work to proceed as rapidly as possible while prohibiting illegitimate work. Part of the problem is it is a new area of medicine where the regulations didn’t anticipate this sort of thing. The regulators on the ground in the field, they themselves don’t have adequate background to tell what’s legit and what’s not. It’s hard.”

Stem cell stories that caught our eye: getting the right cell, an energy booster, history of controversy and a fun video

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.

Light used to direct stem cell fate. Stem cells respond to a symphony of cellular signals telling them to remain stem cells or to mature into a specific type of tissue. Much of stem cell biology today has researchers hitting various notes in various rhythms until the score produces a reasonable percentage of the desired tissue.

It’s often a rather discordant process because the cell is not a simple keyboard. A team at the University of California, San Francisco, has used a neat light trick to make the music a little easier to understand. They started with two known facts: that the protein made by the BRN2 gene can drive stem cells to become nerves and that the gene is often turned on in stem cells and they ignore it, choosing to remain stem cells. The UCSF team genetically engineered mouse stem cells so that they could turn on the BRN2 gene with light.

They found that the gene could only drive the production of nerve cells when it was turned on for a relatively long time. They then discovered that the stem cells were responding to another note in the score, a protein that kept the cells in the stem cell state but became depleted after a prolonged period of BRN2 expression.

“There’s lots of promise that we can do these miraculous things like tissue repair or even growing new organs, but in practice, manipulating stem cells has been notoriously noisy, inefficient, and difficult to control,” said Mather Thomson, one of the senior authors on the paper published in Cell Systems and quoted in a university press release widely picked up, including by News Medical. “I think it’s because the cell is not a puppet. It’s an agent that is constantly interpreting information, like a brain. If we want to precisely manipulate cell fate, we have to understand the information-processing mechanisms in the cell that control how it responds to the things we’re trying to do to it.”

Stem cells delivering engines. Jan Nolte, one of our grantees at the University of California, Davis, and editor of the journal Stem Cells, likes to refer to mesenchymal stem cells (MSCs) as little ambulances that rush emergency medical kits to sites of injury. These stem cells that normally hang out in the bone marrow can generate bone, cartilage and blood vessels, but also can deliver a number of chemicals that either tamp down inflammation or summons other repair cells to the scene. The Scientist published a good overview on how MSCs deliver a key repair tool: mitochondria, known as the powerhouse of cells, to cells in need of an energy boost.

Mitochondria are very susceptible to stressors like a heart attack and often are the first parts of a cell to succumb to the stress. While researchers have known for a decade that MSCs can deliver mitochondria to cells, they haven’t known how this happens. They are rapidly gathering that knowledge hoping they to find better ways to harness that particular MSC skill for therapy.

The author walks through a number of discoveries over the past couple years that have begun to paint a picture of this paramedic skill. She also briefly discusses some potential therapies that have been tested in animals.

Embryonic stem cell controversy waning. Pacific Standard, which has become my favorite “thought” magazine even though I have never seen a print copy, published a pretty thorough overview of the early controversy about embryonic stem cells (ESCs) and the many recent scientific advances that may make them unnecessary. The author closes with the fact that for now, advancing those alternatives requires the continued use of ESCs.

Leading with the George W. Bush quote about ESCs being “the leading edge of a series of moral hazards,” he goes on to note that the controversy drove the creation of CIRM and helped Democrats take control of the Senate in 2006. But the bulk of the piece focuses on the alternatives starting with the Nobel Prize-winning discovery of reprogramed adult cells called induced pluripotent stem cells that mimic ESCs. It also covers most recent advances in converting one type of adult cell directly into another type of tissue.

The author closes with a caveat on the ongoing importance of ESCs, at least for now.

“The controversy isn’t over quite yet though—while the newer techniques are immediately useful in research, they have yet to yield any therapies. And because embryonic stem cells are useful for studying how different types of cells develop naturally in the body, they still play an important role in ongoing biomedical research.”

However, he does suggest that eventually, technology will end this controversy.

NOVA video on imagingNOVA video on the brain. Alright, this video only tangentially relates to stem cells and only mentions them toward the end. But it does get at one of the pressing problems in advancing our field: actually seeing what stem cells do at the cell-to-cell and molecular level.

If you are even a casual fan of science, how can you not like a video that starts out with two young scientists using phrases like, “crazy idea,” “wild dream” and “told we’re wasting our time.” It even goes on to talk about “your brain on diapers.” It’s got to be worth the five and a half minutes on the NOVA PBS web site.

It let’s two MIT researchers narrate their effort to image the tiniest of cellular interactions in the brain. Since they found limitations in every existing attempt to see smaller detail, they decided to inflate the brain and make the details larger. They did this by adding the same absorbent material found in diapers to thin slices of mouse brain that had different types of tissues dyed in varying colors. When they added water the brain slice swelled expanding the details.

The result: some really cool images and a tool already being used by scientists around the world. It is now called “expansion microscopy.”

Stem cell stories that caught our eye: A groove for healing hearts, model for muscular dystrophy and the ice bucket worked

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 tight groove could help heal a heart.  We have written several posts with the theme “It takes a village to raise a stem cell.” If you want a stem cell to mature into a desired tissue you have to pay attention to all aspects of its environment—both the chemicals around it and the physical space.

A team at the Imperial College London has provided the latest chapter to this tale. It turns out if you want stem cells to consistently turn into long fibers of heart muscle, besides providing them with the right chemical signals making them grow in long narrow grooves on lab plate also helps. They got a two-fold increase in heart muscle cells compared to stem cells grown on a flat lab plate.

They’re now trying to figure out why the etched silicon chips worked so well for generating heart muscle. The journal Biomaterials and Regenerative Medicine published the work and the web portal myScience picked up the university’s press release.

Stem cell model for muscular dystrophy. In the past, when scientists have looked at muscle samples from patients with Duchenne muscular dystrophy (DMD) to see why they have the characteristic muscle weakening, they ‘ve arrived at the scene of the crime too late. At that point, the cellular missteps had already occurred and all that is left to observe was the damage.

Healthy muscle cells express dystrophin (green), not cells from DMD patients (middle), but treated stem cells from patients do (right)

Healthy muscle cells express dystrophin (green), not cells from DMD patients (middle), but treated stem cells from patients do (right)

So, a team at Kyoto University reprogrammed a patient’s cells to create iPS type stem cells. They then used genetic cues to direct the stem cells to become muscle and watched to see how what went wrong as this process happened.

“Our model allows us to use the same genetic background to study the early stage of pathogenesis which was not possible in the past,” said first author Emi Shoji.

The research published in Scientific Reports and highlighted in a university press release picked up by MedicalXpress documented the level of inappropriate influx of calcium into the cells and showed that a specific cell surface receptor channel was to blame. That receptor will now become a target for new drug therapy for DMD pateints.

Ice bucket results.  The ALS Association raised $220 million in the past year for amyotrophic lateral sclerosis, or Lou Gehrig’s disease, by getting people to dump bucket of ice water over their heads and then make a donation. More important, in just a year a major paper funded by the proceeds of the ice bucket challenge has shown a defect in the nerves of ALS patients and shown that correcting the defect makes the cells healthier. Those are pretty fast results for science.

In a paper published in the prestigious journal Science a team at Johns Hopkins found that one protein, TDP-43, was not doing its job well. When they genetically modified stem cell from ALS patients to correct that defect the cells worked properly. YahooFinance ran a story about the challenge and the new research.

“If we are able to mimic TDP-43’s function in the human neurons of ALS patients, there’s a good chance that we could slow down progression of the disease!” said Jonathan Ling, a researcher on the team. “And that’s what we’re putting all our efforts into right now.”

Of the initial $115 million raised during the early months of the challenge, 67 percent went to research, 20 percent to patient services, and nine percent to public and professional education. Just four percent went to overhead costs of fund raising.

China says it’s cracking down on clinics. I spend a considerable amount of time suggesting callers to our agency be very cautious about considering spending large sums of money to go overseas to get unregulated and unproven stem cell treatment. So, I was pleased to read this morning’s news that China’s top health authority issued regulation to control some of the most questionable clinics.

The regulations reported in China Daily note that any treatments using stem cells for conditions other than proven uses in blood diseases would be considered experimental and could only be conducted in approved hospitals. It noted conditions touted by clinics there including epilepsy, cerebral palsy, spinal cord injury and autism.

“Only eligible hospitals can perform the practice as a clinical trial for research purpose and it must not be charged or advertised. Anyone caught breaking the rules will be punished according to the new regulation,” said Zhang Linming, a senior official of the science and technology department of the commission.