Shape-Shifting Pancreas Cells Set Stage for Development of Deadly Cancer

After being diagnosed with pancreatic cancer, the likely outcome is—in a word—bleak. At a time when cancers can be treated so successfully as to give the patient a good quality of life, pancreatic cancer remains one of the last holdouts. It is the fourth most deadly form of cancer in the United States. One in four patients won’t last a year.

Pancreatic cancer is one of the most deadly forms of cancer.

Pancreatic cancer is one of the most deadly forms of cancer.

One of the main hurdles for successfully treating this type of cancer is how quickly it spreads. Oftentimes, pancreatic cancer is not diagnosed until having spread to such an extent that even the most aggressive treatments can only delay the inevitable.

As a result, the goal of researchers has been to peer back in time to the origins of pancreatic cancer—in the hopes that they can find a way to halt the disease before it begins to wreak irreversible damage on the body. And now, an international team of researchers believes they have identified a gene that could be the key culprit.

Reporting in the latest issue of Nature Communications, a joint team of scientists from the Mayo Clinic and the University of Oslo, Norway, have pinpointed a gene—called PKD1—that causes normal, healthy pancreatic cells to literally morph into a new, duct-like cell structure. And it is this change in shape that can sometimes lead to pancreatic cancer.

“As soon as pancreatic cancer develops, it begins to spread, and PKD1 is key to both processes,” said Peter Storz, one of the study’s lead authors, in a news release. “Given this finding, we are busy developing a PKD1 inhibitor that we can test further.”

The purpose of the inhibitor, says Storz, is to neutralize PKD1—stopping the cancer in its tracks.

Using pancreatic cells derived from mouse models, the research team tested the effects of PKD1 by turning it on and off at specific intervals, similar to flipping a light switch. In the presence of PKD1, the team observed the pancreas cells rapidly changing shape into the more dangerous, duct-like cells. And when they shut off PKD1, the percentage of cells that underwent shape shifting dropped.

The team’s success at developing this model cannot be understated. As Storz explained:

“This model tells us that PKD1 is essential for the initial transformation…to duct-like cells, which can then become cancerous. If we can stop that transformation from happening—or perhaps reverse the process once it occurs—we may be able to block or treat cancer development and its spread.”

Currently, the teams are developing potential PDK1 inhibitors for further testing—and bring some hope that the prognosis for pancreatic cancer may not always be so dire.

Said Storz: “While these are early days, understanding one of the key drivers in this aggressive cancer is a major step in the right direction.”

Clearing up chemobrain: cancer therapy-induced memory problems reversed by stem cells

You’d think receiving a cancer diagnosis and then suffering through chemo and/or radiation therapy would be traumatic enough. But as many as 75% of cancer survivors are afflicted by memory and attention problems long after their cancer therapy.

This condition, often called “chemobrain”, shouldn’t be misunderstood as being confined to cancers of the brain. A 2012 analysis of nearly 200 women who had been treated with chemotherapy for breast cancer showed they had ongoing memory and information processing deficits that persisted more than twenty years after their last round of treatment. And young cancer survivors are particularly vulnerable to reduced IQs, nonsocial behavior and an extremely lowered quality of life.

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CIRM grantee and UC Irvine professor Charles Limoli, PhD is senior author of this study

Chemotherapy drugs work by killing off cells that are dividing rapidly, a hallmark of cancer cells. But this brute force method also kills other rapidly dividing cells that are critical for normal bodily functions. In the case of chemobrain, it’s thought that damage to newly formed brain cells in the hippocampus, the memory center of the brain, is the culprit. A UC Irvine study published this week in Cancer Research supports that idea in experiments that test the effect of transplanting human nerve stem cells in rats. The research team leader Charles Limoli, a CIRM grantee and UC Irvine professor of radiation oncology, summarized the groundbreaking results in a press release (note: this study is not funded by CIRM):

“Our findings provide the first solid evidence that transplantation of human neural stem cells can be used to reverse chemotherapeutic-induced damage of healthy tissue in the brain.”

The novel place recognition test is evaluate memory function. Animal is initially presented with identical objects (red circles). Then a new object is introduced (blue square). A healthy mouse will investigate the blue square.

The novel place recognition test, one of several tests used in this study to evaluate memory function.  During training setup (left), the rodent is familiarized with identical objects (red circles). Later, rodent returns now in presence of a new object (blue square). A healthy mouse will investigate the new object during testing setup (right). Image credit: KnowingNeurons.com

So how the heck do you observe chemotherapy-induced cognitive problems in a rodent let alone show that stem cells can rescue the damage? In the study, the rats undergo a variety of recognition memory tasks after a typical chemotherapy drug treatment. For instance, in the novel place recognition test, an animal is familiarized with two identical objects inside a test “arena”. Later, the animal is returned to the arena but a new object is swapped in for one of the previous objects. Rats given chemotherapy treatment but no stem cell surgery (they’re implanted with a saline solution instead) do not show a preference for the novel object. But rats given chemotherapy and the human nerve stem cell surgery prefer the novel object. This novel seeking behavior is also seen in control rats given no chemotherapy. So these results demonstrate that the transplanted stem cells rescued normal memory recognition in the chemotherapy-treated rats.

The research team also saw differences within the brains of these groups of rats that match up with these behavioral results. First, they confirmed that the transplanted human stem cells had indeed survived and grafted into the rat brains and had matured into the correct type of brain cells. Next they looked at chemotherapy-induced inflammation of brain tissue. The brains of chemotherapy-treated rats with no stem cell transplantation showed increased number of active immune cells compared to the control and stem cell transplanted animals. In another experiment, a detailed analysis of the structure of individual nerve cells showed extensive damage in the chemotherapy treated rats compared to controls. Again, this damage was reversed in chemotherapy treated rats that also received the stem cell transplant.

Rat nerve cells (black structures) in memory center of the brain are damaged by chemotherapy (left); transplanting human nerve stem cells reverses the damage (right)

Rat nerve cells (black structures) in memory center of the brain are damaged by chemotherapy (left); transplanting human nerve stem cells reverses the damage (right). Image credit: Acharya et al. Cancer Research 75(4) p. 676

As many researchers can tell you, these exciting results in animals don’t guarantee a human therapy is around the corner. But still, says Limoli:

“This research suggests that stem cell therapies may one day be implemented in the clinic to provide relief to patients suffering from cognitive impairments incurred as a result of their cancer treatments. While much work remains, a clinical trial analyzing the safety of such approaches may be possible within a few years.”

For a more details about the role of stem cells in chemobrain, watch this recent presentation to the CIRM Governing Board by CIRM grantee and Stanford professor Michelle Monje.

Combination Cancer Therapy Gives Cells a Knockout Punch

For some forms of cancer, there really is no way to truly eradicate it. Even the most advanced chemotherapy treatments leave behind some straggler cells that can fuel a relapse.

By hitting breast cancer cells with a targeted therapeutic immediately after chemotherapy, researchers were able to target cancer cells during a transitional stage when they were most vulnerable. [Credit: Aaron Goldman]

By hitting breast cancer cells with a targeted therapeutic immediately after chemotherapy, researchers were able to target cancer cells during a transitional stage when they were most vulnerable.
[Credit: Aaron Goldman]

But now, scientists have devised a unique strategy, something they are calling a ‘one-two punch’ that can more effectively wipe out dangerous tumors, and lower the risk of them ever returning for a round two.

Reporting in the latest issue of the journal Nature Communications, bioengineers at Brigham and Women’s Hospital (BWH) in Boston describe how treating breast cancer cells with a targeted drug immediately after chemotherapy was effective at killing the cancer cells and preventing a recurrence. According to lead scientist Shiladitya Sengupta, these findings were wholly unexpected:

“We were studying the fundamentals of how [drug] resistance develops and looking to understand what drives [cancer] relapse. What we found is a new paradigm for thinking about chemotherapy.”

In recent years, many scientists have suggested cancer stem cells are one of the biggest hurdles to curing cancer. Cancer stem cells are proposed to be a subpopulation of cancer cells that are resistant to chemotherapy. As a result, they can propagate the cancer after treatment, leading to a relapse.

In this work, Sengupta and his colleagues treated breast cancer cells with chemotherapy. And here is where things started getting interesting.

After chemotherapy, the breast cancer cells began to morph into cells that bore a close resemblance to cancer stem cells. For a brief period of time after treatment, these cells were neither fully cancer cells, nor fully stem cells. They were in transition.

The team then realized that because these cells were in transition, they may be more vulnerable to attack. Testing this hypothesis in mouse models of breast cancer, the team first zapped the tumors with chemotherapy. And, once the cells began to morph, they then blasted them with a different type of drug. The tumors never grew back, and the mice survived.

Interestingly, the team did not have similar success when they altered the timing of when they administered the therapy. Treating the mice with both types of drugs simultaneously didn’t have the same effect. Neither did increasing the time between treatments. In order to successfully treat the tumor they had a very slim window of opportunity.

“By treating with chemotherapy, we’re driving cells through a transition state and creating vulnerabilities,” said Aaron Goldman, the study’s first author. “This opens up the door: we can then try out different combinations and regimens to find the most effective way to kill the cells and inhibit tumor growth.”

In order to test these combinations, the researchers developed an ‘explant,’ a mini-tumor derived from a patient’s biopsy that can be grown in an environment that closely mimics its natural surroundings. The ultimate goal, says Goldman, is to map the precise order and timing of this treatment regimen in order to move toward clinical trials:

“Our goal is to build a regimen that will be [effective] for clinical trials. Once we’ve understood specific timing, sequence of drug delivery and dosage better, it will be easier to translate these findings clinically.”

Stem cell stories that caught our eye: repairing radiation damage, beta thalassemia clinical trial and disease models

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 repair brain damage from radiation therapy. Radiation for brain cancer can be a lifesaver but it can also be a dramatic life changer. If often leaves patients with considerably reduced brain function. Now a team at New York’s Memorial Sloan Kettering Cancer Center has found a way to instruct human stem cells to repair some of that damage—at least in rats.

The damage seems to be to the middle-man or so-called progenitor cells that maintain the myelin cells that insulate the nerves in the brain. When that myelin is damaged by the radiation those progenitor cells are no longer able to make repairs and that results in reduced nerve function. Rats given the stem cells regained both cognitive and motor skills lost after brain radiation.

The team leader, Viviane Taber, noted this work could make radiation therapy even more of a lifesaver. ScienceDaily quoted Tabar from materials provided by Cell Press that published the work:

“This will have to be proven further, but if we can repair the brain effectively, we could be bolder with our radiation dosing, within limits.”

This could be especially important in children, for whom physicians deliberately deliver lower radiation doses.


Stem cell trial for Beta-Thalassemia cleared to begin.
CIRM-grantee Sangamo BioSciences announced this week that the Food and Drug Administration (FDA) had accepted its application to begin a clinical trial using genetically edited stem cells to treat patients with beta-thalassemia. This trial, in patients who require regular blood transfusions to survive, is the ninth CIRM-funded clinical trail to gain clearance from the FDA.

Other clinical trials have used genetically modified stem cells, but they have used various techniques to add a correct gene or silence an unwanted gene. This will be the first clinical trial using one of the newer techniques that actually goes into a person’s genes and edits them to correct a disease. We wrote about this beta-thalassemia project here.

The Sacramento Business Times picked up the company’s press release that quoted Sangamo president Edward Lanphier on the company’s goal, “the aim of providing transfusion-dependent beta-thalassemia patients with a one-time treatment for this devastating disease.”

Disease modeling for science wonks. Vivien Marx wrote a feature article for Nature Methods that provides the most thorough review of the use of reprogramed iPS-type stem cells as disease models that I have read. In particular she discusses the power of using new gene editing tools to modify the cells so that when they mature into adult tissues they will display specific disease traits.

Svendsen hopes to use gene-edited iPS type stem cells to fully understand neurodegenerative diseases

Svendsen hopes to use gene-edited iPS type stem cells to fully understand neurodegenerative diseases

She starts with a narrative about CIRM-grantee Clive Svendsen’s work to understand spinal muscular atropohy (SMA) when he was in Wisconsin and to understand amyotrophic lateral sclerosis (ALS) now at Cedars Sinai in Los Angeles. She goes on to show just how powerful these gene-edited stem cells can be, but also how difficult it is to use the technology in a way that generates useful information. Marx is a strong science journalist, who for many years has shown a skill at explaining complex technologies.

She also discusses the various iPS cell banks developed around the world including CIRM’s cell bank and the value of having non-gene-edited cells from patients that naturally show the disease traits.

Thorough review of changes at CIRM.
Alex Lash at xconomy wrote an in-depth overview of our president Randy Mills’ plans for the next phase of our agency that Randy calls CIRM 2.0. Calling the plans an extensive “renovation” Lash described the portions of the new structure that were already in place and listed the ones set to come online in the next six months.

As a balanced journalist he runs through some of the highs and lows of our public perception during the initial phase of the agency and then discusses the new tone set by Mills:

“CIRM is less a grant-making government agency than a ‘discerning investor’ that’s going to be ‘as creative and innovative’ as possible in getting treatments approved, Mills says. ‘We have no mission above accelerating stem cell therapies to patients.’ ”

In living color: new imaging technique tracks traveling stem cells

Before blood stem cells can mature, before they can grow and multiply into the red blood cells that feed our organs, or the white blood cells that protect us from pathogens, they must go on a journey.

A blood stem cell en route to taking root in a zebrafish. [Credit: Boston Children's Hospital]

A blood stem cell en route to taking root in a zebrafish. [Credit:
Boston Children’s Hospital]

This journey, which takes place in the developing embryo, moves blood stem cells from their place of origin to where they will take root to grow and mature. That this journey happened was well known to scientists, but precisely how it happened remained shrouded in darkness.

But now, for the first time, scientists at Boston Children’s Hospital have literally shone a light on the entire process. In so doing, they have opened the door to improving surgical procedures that also rely on the movement of blood cells—such as bone marrow transplants, which are in essence stem cell transplants.

Reporting in today’s issue of the journal Cell, Boston Children’s senior investigator Leonard Zon and his team developed a way to visually track the trip that blood stem cells take in the developing embryo. As described in today’s news release, the same process that guides blood stem cells to the right place also occurs during a bone marrow transplant. The similarities between the two, therefore, could lead to more successful bone marrow transplants. According to the study’s co-first author Owen Tamplin:

“Stem cell and bone marrow transplants are still very much a black box—cells are introduced into a patient and later on we can measure recovery of the blood system, but what happens in between can’t be seen. Now we have a system where we can actually watch that middle step.”

And in the following video, Zon describes exactly how they did it:

As outlined in the above video, Zon and his team developed a transparent version of the zebrafish, a tiny model organism that is often used by scientists to study embryonic development. They then labeled blood stem cells in this transparent fish with a special fluorescent dye, so that the cells glowed green. And finally, with the help of both confocal and electron microscopy, they sat back and watched the blood stem cell take root in what’s called its niche—in beautiful Technicolor.

“Nobody’s ever visualized live how a stem cell interacts with its niche,” explained Zon. “This is the first time we get a very high-resolution view of the process.”

Further experiments found that the process in zebrafish closely resembled the process in mice—an indication that the same basic system could exist for humans.

With that possibility in mind, Zon and his team already have a lead on a way to improve the success of human bone marrow transplants. In chemical screening experiments, the team identified a chemical compound called lycorine that boosts the interaction between the zebrafish blood stem cell and its niche—thus promoting the number of blood stem cells as the embryo matures.

Does the lycorine compound (or an equivalent) exist to boost blood stem cells in mice? Or even in humans? That remains to be seen. But with the help of the imaging technology used by Zon and the Boston Children’s team—they have a good chance of being able to see it.

Stem cell stories that caught our eye: EU approves a cell therapy, second ALS treatment shows promise and new gut cells work

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.

Europe approves first 2nd generation stem cell therapy.
While blood stem cells in bone marrow have been used to treat patients with certain blood cancers for more than 40 years, it has been a long wait for other uses of stem cells to gain official nods from regulatory bodies. The first came in 2012 when Canada approved Prochymal a stem cell therapy for kids who have a severe immune reaction after bone marrow transplant for cancer. That therapy helps the patients regulate their immune response and can be life saving.

Now the European Medicines Agency has approved a therapy for repairing eyes with damaged corneas—the first of a new generation of stem cell therapies that replace or repair specific tissues. The therapy uses a type of stem cell found in the eye called a limbal stem cell. An Italian team pioneered the procedure that has successfully restored vision to scores of patients whose eyes were damaged by chemicals or burns. An official with the EMA noted the significance of this approval in an agency press release.

“This recommendation represents a major step forward in delivering new and innovative medicines to patients.”

The BBC broke the news with a brief story, and MSN followed up with a bit more detail. (And no, this did not happen “this week” but it did happen after we went dark for the holidays.) CIRM also funds work with limbal stem cells.

Second type of stem cells shows benefit for ALS patients. Over the past couple years we have been writing about positive early trial results from Neuralstem for its therapy using a nerve stem cell for treating patients with ALS, also called Lou Gehrig’s disease. This week the company Brainstorm reported data showing improvement in most of the patients treated with a type of stem cell found in bone marrow and fat, mesenchymal stem cells.

The Neuralstem trials used donor stem cells and the Brainstorm trial uses a patient’s own cells, hence the drug name NeuOwn. But they have be revved up in the lab so that they secrete large quantities of what are called neurotrophic factors, chemicals that seem to protect nerves from damage by the disease and potentially foster healing of already damaged nerves.

Eleven of 12 patients experienced a decrease in the rate of progression of this normally very aggressive disease. The Israeli company completed its early trials in Israel but began a second stage trial at Massachusetts General Hospital in April. Reuters ran a story about the announcement.

New intestine engineered from stem cells. CIRM-grantee Tracy Grikscheit has previously reported growing tissues that look like intestinal cells and that have all the right cellular dog tags of our guts. Today the university announced she has shown she can grow tissues that actually function like our guts. They can absorb life-sustaining nutrients.

Because her work focuses on the devastating condition that results when a baby is born with insufficient intestine, it was not surprising this morning to find a good story about her work on the web site MotherBoard. The site quotes her on the latest advance:

“What’s important about this study is it’s not just taking pictures of the cells and saying ok, they’re in the proper location. We’re actually also looking at the function, so we’re showing that not only are the cells present that would for example absorb the sugar in your breakfast, but they actually are doing that job of absorbing sugar.”

Grikscheit works at Children’s Hospital Los Angeles and you can read about her CIRM-funded work to build new intestine here.


Luck’s role in stem cell mutations key to cancer.
Most of the popular talk about risk and cancer centers on inheriting bad genes and being exposed to nasty chemicals in our daily lives. But a new study says the biggest risk is more akin to a roulette wheel.

A study published in Science by a team at Johns Hopkins looked at 31 types of tissue in our bodies and found that random mutations that occur while our tissue-specific stem cells divide correlates better with cancer risk than what we inherit or environmental risks combined. The Scientist produced one of the more thoughtful pieces of the many on the research that appeared in the media this week.

A personal story about getting into stem cell research. I enjoy hearing about how people get into this fascinating field and the media team at the University of Southern California has provided a good example. They profile recent recruit, Michael Bonaguidi who explains how he made the switch from physical to biological science:

“Growing up on Legos and Lincoln Logs, I was very fascinated with building things. As I took more biology courses and was exposed to other facets of science — from chemistry to physics — I became more interested not in the outside but within. And that’s what got me into bioengineering versus structural engineering.”

Described as shaping brains instead of cities he is looking for the types of cells that can rebuild the brain after injury or stroke. HealthCanal picked up the university’s feature.

Scientists identify gene that causes good protein to turn bad

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There exists a protein that, most of the time, helps keep the growth of cancer cells in check. But every so often it does the opposite—with potentially deadly consequences.

But now, researchers have discovered precisely why this protein, known as TGF-beta, can perform such an abrupt about-face. The results, published today in the journal Science Signaling, shed light on potential therapies that can succeed where others have failed—and attack the most aggressive forms of cancer.

TGF-beta is a type of tumor suppressor, a protein that normally keeps cells from growing, dividing and multiplying too quickly, which is how most tumors originate. But scientists have long observed that in many forms of cancer, TGF-beta has switched sides: it becomes a tumor promoter fostering the out-of-control growth of cells.

In this study, scientists at the University of Michigan Comprehensive Cancer Center have figured out that a gene called Bub1 seems to be pulling the strings—essentially flipping the switch on TGF-beta. The finding that Bub1 played such an important role in regulating TGF-beta caught the team completely off guard. According to the paper’s senior author Alnawaz Rehemtulla:

“Bub1 is well-known for its role in cell division. But this is the first study that links it to TGF-beta. We think this may explain the paradox of TGF-beta as a tumor promoter and a tumor suppressor.”

The team reached this conclusion by screening gene candidates against lung cancer and breast cancer cells. After screening over 700 genes, they narrowed down the potential gene to Bub1.

Further experiments revealed that Bub1 physically binds to TGF-beta, turning it to a tumor promoter in the process. And when the team prevented Bub1 from binding to TFG-beta, essentially blocking it, TGF-beta never turned sides.

These initial results have left the research team optimistic, in large part because Bub1 is known to be active, or ‘expressed,’ in so many forms of cancer. So, if they can find a way to block Bub1 in one type of cancer, they may be able to do so with other types.

Even at this early stage, the team has developed a compound that could block Bub1. Initial lab tests show that this so-called Bub1 ‘inhibitor’ could shut off the gene without affecting surrounding regions. Said Rehemtulla:

“When you look at gene expression in cancer, Bub1 is in the top five…. But we never knew why. Now that we have that link, we’re a step closer to shutting down this cycle.”

Stem Cell Stories that Caught Your Eye: The Most Popular Stem Cellar Stories of 2014

2014 marked an extraordinary year for regenerative medicine and for CIRM. We welcomed a new president, several of our research programs have moved into clinical trials—and our goal of accelerating treatments for patients in need is within our grasp.

As we look back we’d like to revisit The Stem Cellar’s ten most popular stories of 2014. We hope you enjoyed reading them as much as we did reporting them. And from all of us here at the Stem Cell Agency we wish you a Happy Holidays and New Year.

10. UCSD Team Launches CIRM-Funded Trial to Test Safety of New Leukemia Drug

9. Creating a Genetic Model for Autism, with a Little Help from the Tooth Fairy

8. A Tumor’s Trojan Horse: CIRM Researchers Build Nanoparticles to Infiltrate Hard-to-Reach Tumors

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

6. New Videos: Living with Crohn’s Disease and Working Towards a Stem Cell Therapy

5. Creativity Program Students Reach New Heights with Stem Cell-Themed Rendition of “Let it Go”

4. Scientists Reach Yet Another Milestone towards Treating Type 1 Diabetes

3. Meet the Stem Cell Agency President C. Randal Mills

2. Truth or Consequences: how to spot a liar and what to do once you catch them

1. UCLA team cures infants of often-fatal “bubble baby” disease by inserting gene in their stem cells; sickle cell disease is next target

Stem cell stories that caught our eye: organ replacement, ovarian cancer and repairing damaged hearts.

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.

Numbers on organ shortage and review of lab replacements.
Vox, the four-month-old web site, is rapidly becoming a credible news source with more than five million page views so far. With a reputation for explaining the facts behind the news, it was nice to see they tackled the organ shortage and how researchers are using stem cells to try to solve it.

organ shortage.0After providing data on the incredible need, the author addressed several key advances, as well as remaining hurdles, to using stem cells to build replacement organs in the lab. She notes that an important step to growing an organ is being able to grow all the various types of cells that make up a complex organ.

“Each specialized type of cell in your body needs certain chemical clues from its environment in order to thrive and multiply. And even a simple-seeming body part, like a urethra, requires more than one cell type, arranged in certain ways relative to one another.”

In addition to a chart with data on organ donation and need, the article provides a link to a fun video on growing a rat lung in the lab. The author closes with the fact that the greatest need is for kidneys and a discussion of how tough they are to make because of the complex mix of tissues needed.

An advance in building kidneys also made the journals this week, with a press release from Cellular Dynamics describing how their lab grown cells succeeded in coating the inside of blood vessels in a scaffold for a rodent kidney.

Stem cell factors heal damaged hearts. The American Heart Association met in Chicago this week and as always the week of their fall enclave generates several news stories. Genetic Engineering & Biotechnology News wrote up a study from the Icahn School of Medicine at Mount Sinai in New York that suggested how your own stem cells might be recruited to repair damage after a heart attack.

The New York team used a form of gene therapy that introduced the genes for “stem cell factors” that they believe could summon a type of stem cell that some have suggested can repair heart muscle. Although, whether those cells, called c-Kit positive heart stem cells, are actually the cause of the repair remains a subject of debate. They did show that their treatment improved heart function and decreased heart muscle death in the rodent model they were using.

Stem cells improve survival of skin grafts.
With so many soldiers returning from deployments needing reconstructive surgery, several teams at our armed services medical institutes are trying to solve the problem of the soldiers’ immune systems rejecting large skin grafts from donors. One team reported a potentially major advance in the Journal Stem Cells Translational Medicine and the web site benzinga picked up the journal’s press release.

Working in mice the team got the best skin graft survival in animals that received two types of stem cells to induce immune tolerance to the graft. The mice received fat-derived stem cells from humans and an infusion of a small number of their own bone marrow stem cells. The grafts showed no sign of rejection after 200 days, a very long time in a mouse’s life. In the press release, the editor of the journal, Anthony Atala, suggested the results could have broad implications for the field.

“The implications of this research are broad. If these findings are duplicated in additional models and in human trials, there is potential to apply this strategy to many areas of transplantation.”

Leukemia drug may also work in ovarian cancer. The antibody named for CIRM in recognition of our funding of its discovery, cirmtuzumab, which is already in clinical trials in humans for leukemia, may also be effective in one of the most stubborn tumors, ovarian cancer.

Ovarian cancer cells

Ovarian cancer cells

The University of California, San Diego, team led by Thomas Kipps published a study in the Proceedings of the National Academy of Sciences this week showing that in mice the antibody kept transplanted human ovarian cancer cells in check. The tumor that is characterized by rapid spread did not metastasize at all. HealthCanal picked up the university’s press release explaining how the new drug works. You can read about the CIRM-funded clinical trial in leukemia in our fact sheet.

Versatile fingernail stem cells.
The stem cells that regrow our nails are prodigious little critters forcing us to constantly cut or file. But it turns out they are also versatile. They can stimulate nail growth but also growth of skin around the nail.

But if our nails get injured they become single minded and only make nail cells. A team at the University of Southern California has discovered that at the time of injury a particular protein signal gets turned on directing the stem cells to focus on the nails. So, the team is now looking for other signaling proteins that might direct these versatile cells to make other tissues making them potential tools for healing amputations. ScienceDaily picked up the university’s press release.

Don Gibbons

10 Years/10 Therapies: 10 Years after its Founding CIRM will have 10 Therapies Approved for Clinical Trials

In 2004, when 59 percent of California voters approved the creation of CIRM, our state embarked on an unprecedented experiment: providing concentrated funding to a new, promising area of research. The goal: accelerate the process of getting therapies to patients, especially those with unmet medical needs.

Having 10 potential treatments expected to be approved for clinical trials by the end of this year is no small feat. Indeed, it is viewed by many in the industry as a clear acceleration of the normal pace of discovery. Here are our first 10 treatments to be approved for testing in patients.

HIV/AIDS. The company Calimmune is genetically modifying patients’ own blood-forming stem cells so that they can produce immune cells—the ones normally destroyed by the virus—that cannot be infected by the virus. It is hoped this will allow the patients to clear their systems of the virus, effectively curing the disease.

Spinal cord injury patient advocate Katie Sharify is optimistic about the latest clinical trial led by Asterias Biotherapeutics.

Spinal cord injury patient advocate Katie Sharify is optimistic about the clinical trial led by Asterias Biotherapeutics.

Spinal Cord Injury. The company Asterias Biotherapeutics uses cells derived from embryonic stem cells to heal the spinal cord at the site of injury. They mature the stem cells into cells called oligodendrocyte precursor cells that are injected at the site of injury where it is hoped they can repair the insulating layer, called myelin, that normally protects the nerves in the spinal cord.

Heart Disease. The company Capricor is using donor cells derived from heart stem cells to treat patients developing heart failure after a heart attack. In early studies the cells appear to reduce scar tissue, promote blood vessel growth and improve heart function.

Solid Tumors. A team at the University of California, Los Angeles, has developed a drug that seeks out and destroys cancer stem cells, which are considered by many to be the reason cancers resist treatment and recur. It is believed that eliminating the cancer stem cells may lead to long-term cures.

Leukemia. A team at the University of California, San Diego, is using a protein called an antibody to target cancer stem cells. The antibody senses and attaches to a protein on the surface of cancer stem cells. That disables the protein, which slows the growth of the leukemia and makes it more vulnerable to other anti-cancer drugs.

Sickle Cell Anemia. A team at the University of California, Los Angeles, is genetically modifying a patient’s own blood stem cells so they will produce a correct version of hemoglobin, the oxygen carrying protein that is mutated in these patients, which causes an abnormal sickle-like shape to the red blood cells. These misshapen cells lead to dangerous blood clots and debilitating pain The genetically modified stem cells will be given back to the patient to create a new sickle cell-free blood supply.

Solid Tumors. A team at Stanford University is using a molecule known as an antibody to target cancer stem cells. This antibody can recognize a protein the cancer stem cells carry on their cell surface. The cancer cells use that protein to evade the component of our immune system that routinely destroys tumors. By disabling this protein the team hopes to empower the body’s own immune system to attack and destroy the cancer stem cells.

Diabetes. The company Viacyte is growing cells in a permeable pouch that when implanted under the skin can sense blood sugar and produce the levels of insulin needed to eliminate the symptoms of diabetes. They start with embryonic stem cells, mature them part way to becoming pancreas tissues and insert them into the permeable pouch. When transplanted in the patient, the cells fully develop into the cells needed for proper metabolism of sugar and restore it to a healthy level.

HIV/AIDS. A team at The City of Hope is genetically modifying patients’ own blood-forming stem cells so that they can produce immune cells—the ones normally destroyed by the virus—that cannot be infected by the virus. It is hoped this will allow the patients to clear their systems of the virus, effectively curing the disease

Blindness. A team at the University of Southern California is using cells derived from embryonic stem cell and a scaffold to replace cells damaged in Age-related Macular Degeneration (AMD), the leading cause of blindness in the elderly. The therapy starts with embryonic stem cells that have been matured into a type of cell lost in AMD and places them on a single layer synthetic scaffold. This sheet of cells is inserted surgically into the back of the eye to replace the damaged cells that are needed to maintain healthy photoreceptors in the retina.