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

Stem cell stories that caught our eye: gene editing tools, lung repair in COPD and big brains

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.

Correcting the genetic error in sickle-cell disease might be as simple as editing the text.

Correcting the genetic error in sickle-cell disease might be as simple as editing the text [Credit: Nature News].

Review of the many ways to edit defective genes. Nature’s news section did a nice review of the many ways blood-forming stem cells can be genetically altered to correct diseases caused by a single mutation. If you have been following the recently booming field of gene therapy, you may have a hard time keeping all the items in the gene editing toolbox straight. The Nature author provides a rundown on the leading contenders—viral vectors, zinc fingers, TALENs and CRISPRs. Early in the piece she describes why researchers are so excited by the field.

“Although most existing treatments for genetic diseases typically only target symptoms, genetic manipulation or ‘gene therapy’ goes after the cause itself.”

Much of the article talks about work by CIRM grantees. It describes work by Don Kohn at the University of California, Los Angeles, on vectors and zinc fingers, as well as work by Juan Carlos Izpisua Belmonte at the Salk Institute using TALENS and CRISPRs. We explain Kohn’s work treating sickle cell disease in our Fact Sheet.

Getting lungs to repair themselves. A research team at Jackson Labs in Maine has isolated a stem cell in lungs that appears to be able to repair damage left behind by severe infections. They hope to learn enough about how those stem cells work to enlist them to repair damage in diseases like Chronic Obstructive Pulmonary Disease (COPD).

They published the work in Nature and ScienceDaily picked up the lab’s press release. It quotes the lead researcher, Wa Xian on the hope they see down the road for the 12 million people in the U.S. with COPD:

“These patients have few therapeutic options today. We hope that our research could lead to new ways to help them.”

Making middle-man cells more valuable. The University of Wisconsin lab of Jamie Thomson, where human embryonic stem cells (ESCs) were first isolated, has found a way to make some of the offspring of those stem cells more valuable.

We have often written that for therapy, the desired cell to start with is not an ESC or even the end desired adult tissue, but rather a middleman cell called a progenitor. But those cells often don’t renew, or replicate themselves, very well in the lab. Ideally researchers would like to have a steady supply of progenitor cells that could be pushed to mature further only when needed. The Thomson lab found that by manipulating a few genes they could arrest the development of progenitors so they constantly renew themselves. ScienceNewsline picked up the press release from the University’s Morgridge Institute that houses the Thomson lab.

Link found to human’s big brains. A CIRM-funded team at the University of California, San Francisco, isolated a protein that seems to be responsible for fostering the large brain size in humans compared with other animals. Human brain stem cells need the protein, dubbed PDGFD, to reproduce.

The team found that the protein acts on parts of the brain that have changed during mammalian evolution. It is not active at all in mice brains, for example. So, if someone accuses you of being a smart aleck just tell them you can’t help it, it’s your PDGFD. HealthCanal ran the university’s press release, which provides a lot more detail of how the protein actually helps give us big heads.

Don Gibbons

Stem cell stories that caught our eye: heart repair, epilepsy and comparing cloned and reprogrammed cells

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.

Reminding broken hearts how to mend them selves.
After years of tracking down the right genetic buttons a team at the Salk Institute in La Jolla has taught a mammal to do what zebra fish do naturally, repair a severely damaged heart. While all our cells have the genetic code for building whole organs those genes seem to be switched off in all higher animals, but active in some more primitive species like zebra fish and salamanders.

New cells (red) repairing injury in a zebra fish heart.

New cells (red) repairing injury in a zebra fish heart.

Starting a decade ago the researchers measured the gene activity during heart repair in the fish. They found many genes that had their on-off status change during repair. They then looked to see which of those genes had been preserved during evolution to mammal species. They found four genes that were turned off during repair in the fish but were turned on in the mice they were using.

When, with CIRM funding, they inserted genetic signals to turn off those genes in the mice, they saw significant repair of the damaged heart. There are many steps between this advance and getting human hearts to repair them selves—notably finding a way to introduce the genetic signals without using the virus used in this study. HealthCanal picked up the institute’s press release.

Cloned stem cells pretty much like reprogrammed stem cells. In the early days of stem cell research there was a great deal of excitement about the possibility of creating stem cells that genetically match a patient by a process commonly called cloning. This process of taking the genetic storehouse of a cell, the nucleus, and inserting it into a donor egg had been relatively easy in mice. But it turned out quite difficult in humans and was only accomplished last year.

During the years of failed attempts at this process known as nuclear transfer in humans an alternative came into the field. The Nobel prize-winning discovery that you can reprogram any adult cell to act like an embryonic stem cell gave us a new way to create personalized stem cells that genetically match a patient. But ever since that 2008 advance, the research community has fretted over whether those new stem cells called iPS cells really match embryonic stem cells. The iPS cells came from older cells that had lived through many opportunities for mutation and the genetic factors used to reprogram them added further opportunities for mutation.

Researchers at the New York Stem Cell Foundation’s in house lab have now compared the two types of cells with several layers of genetic analysis. They found the same level of mutation in the iPS cells and the cells from nuclear transfer lending some reassurance to the use of iPS cells going forward. HealthCanal ran the foundation’s press release.

A more efficient way to make cloned stem cells. Even though a team in Oregon overcame the obstacles to creating stem cells by nuclear transfer last year, and the feat has been repeated by the New York team above and others, it remains terribly inefficient. So, several groups are working on better ways to make these potentially valuable cells.

A former colleague now at Children’s Hospital, Boston wrote a nice explanation of how researchers are going about making these cloned cells easier in the hospital’s blog, Vector.

Stem cells reduced seizures.
The seizures endured by people with many forms of epilepsy originate from genetic defects in their nerves. So, a team at McClean Hospital outside of Boston implanted healthy nerves grown from embryonic stem cells in mice with genetically linked seizures. Half the mice no longer had seizures and the other half had their seizure frequency reduced.

The type of nerves transplanted are called interneurons, which are known to be the nerves that reduce firing of signals. In epilepsy nerve signals are hyperactive. The team is now working on methods to mature the stem cells into purer populations of just the desired interneurons. ClinicalSpace picked up the hospital’s press release.

Don Gibbons

Ideas and Energy Reveal Surprises at Stem Cell Showcase

Janssen, the company within the pharmaceutical giant Johnson & Johnson responsible for much of its research and development, has a branch in the Bay Area called J Labs. It seeks to foster innovation in all sectors of biomedical research. One piece of that effort brings together innovators for monthly gatherings to exchange ideas and network. The events have an upbeat sense of energy so it was exciting when they invited CIRM to put together an all-day session dubbed: CIRM Showcase: Accelerating Stem Cell Treatments to Patients.

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The resulting showcase yesterday had that energy. But for someone who knows the CIRM portfolio of projects backward and forward, I thought, there were a few pleasant surprises. Perhaps the most exciting news came from Linda Marban, CEO of Capricor, the company CIRM is funding to complete a clinical trial in patients with weakened hearts after a heart attack. She disclosed that the company’s next target is the heart remodeling that is the cause of death in most boys with Duchenne muscular dystrophy. She said some early data would be released at the American Heart Association meeting in Chicago in two weeks.

Another bit of news—most exciting for science wonks—came from the biotech company Sangamo that CIRM funds to develop genetically modified blood stem cells as therapy for two diseases, HIV and beta thalassemia. The firm has developed a molecular scissors called a zinc finger nuclease that can splice the DNA that makes our genes. I knew the technique was pretty precise, but Curt Herberts from the company said they had perfected it to where it could get down to a single base pair—a single link in the chain that makes up our DNA. This greatly reduces the chances for any unintended effects of the genetic manipulation.

Two advances I learned about were in using iPS type stem cells as models for disease and for discovery of traditional drugs to treat those diseases. Ashkan Javaherian, from Steve Finkbeiner’s lab at the Gladstone Institutes, described some results with the robotic microscope they have developed that lets them screen hundreds of molecules on neurons grown from iPS cells reprogrammed from patients with specific diseases. Looking just at compounds already approved by the Food and Drug Administration (FDA), ones that could be put in the clinic quickly, they found four that reduced the degradation normally seen in neurons grown from patients with Huntington’s disease.

Similarly, Joseph Wu of Stanford described his work with cells from families with various genetic heart disorders. In addition to getting individualized information from the patient-specific cells, he said they could now take it one step further and sequence the entire DNA of the cells for just $500, yielding the chance to find out exactly what mutations were causing the disease. He said it was a big step towards truly personalized medicine and to developing therapies for various racial groups that respond differently to drugs.

The day began with our President and CEO C. Randall Mills detailing his plans for a nimbler, more responsive CIRM he has dubbed CIRM 2.0. This crowd seemed thrilled with his plan for an open call for applications so that they could come in with a request when they are ready instead of forcing them into a premature application for funding because the window might not open for another year or two.

One bit of trivia drove home how difficult the entire process of moving innovative therapies into the clinic can be. Paul Laikind, CEO of ViaCyte, the company CIRM has provided more than $50 million to develop a diabetes therapy, noted the size of the application they sent to the FDA: 8,500 pages. Kind of says it all.

Don Gibbons

Stem Cell Stories that Caught our Eye: Perspective on “Walking” Patient, Blood Stem Cells have a Helper and Three Clinical Trials at One Campus

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.

Some perspective on nasal stem cells and ”walking” patient. PZ Meyers writing on ScienceBlogs did a good job of putting some perspective into the hype in many news outlets about the spinal cord injury patient who was treated with nasal stem cells. He starts out admitting he was “incredulous” that there was anything to the study, but after a thorough reading of the actual journal article he was convinced that there was some real, though modest gain in function for the patient. His conclusion:

“Sad to say, the improvements in the man’s motor and sensory ability are more limited and more realistic than most of the accounts would have you think.”

The research team actually reported on three patients. One got barely noticeable improvement; the patient in the news reports regained about 25 percent of function—which is indisputably a major gain in this population—and the third was somewhere in between.

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Meyer speculated about a reason for the improvements that was left out of most press reports. In addition to the stem cell harvested from the patients’ own nasal passages injected on either side of the injury the team also harvested nerve fibers from the patients legs and transplanted them across the site of the injury. They hoped the nerve strands would act as a bridge for the stem cells to grow and close the gap. It is also possible that being nerve cells they could provide the right cell-to-cell signals directing the nasal stem cells to become nerves. Meyers closed with an appropriate summary:

“I think there’s good reason to be optimistic and see some hope for an effective treatment for serious spinal cord injuries, but right now it has to be a realistic hope — progress has been made. A cure does not exist.”

Body’s own helper for blood stem cells found. In a case of the children ordering around the parents, a team at the Stowers Institute in Kansas City found that one of the progeny of blood-forming stem cells in the bone marrow can control the activity of the stem cells. In particular, they were looking at megacarocytes, the relatively rare bone marrow cells that normally produce the blood platelets you need for clotting a wound.

Blood stem cells are the most common stem cell therapy today, but one plagued by our limited ability to control their growth. Knowing this involvement of their offspring gives researcher a new avenue to search for ways to grow the much needed parent stem cells. Genetic Engineering & Biotechnology News wrote up the findings.

(Yes, I may be the only person in World Series-obsessed San Francisco writing something positive about Kansas City this week.)

Three clinical trails launched at just one campus. We have written individually about three clinical trials that began in the last month at the University of California, San Diego. Now, the university has written a good wrap up of the three trials that got posted to ScienceDaily.

Collectively, the three trials show the breadth of stem cell research starting to reach patients. One trial, for diabetes, uses cells derived from embryonic stem cells encased in a pouch to protect them from immune rejection. Another uses cells derived from fetal nerve stem cells to treat spinal cord injury. And the third involves a drug that targets the cancer stem cells that are believed to cause much of the spread of the disease and resistance to chemotherapy in cancer patients.

CIRM is funding two of the three trials and supported much of the basic science that led to the third. We expect to be funding 10 projects with approved clinical trials by the end of the year. The field is moving.

Don Gibbons

Stem cell stories that caught our eye: Some good news got a little overplayed on blindness and Alzheimer’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.

Stories on blindness show too much wide-eyed wonder. While our field got some very good news this week when Advanced Cell Technologies (ACT) published data on its first 18 patients treated for two blinding diseases, many of the news stories were a little too positive. The San Diego Union Tribune ran the story from Associated Press writer Maria Cheng who produced an appropriately measured piece. She led with the main point of this early-phase study—the cells implanted seem to be safe—and discussed “improved vision” in half the patients. She did not imply their sight came back to normal. Her third paragraph had a quote from a leading voice in the field Chris Mason of University College London:

“It’s a wonderful first step but it doesn’t prove that (stem cells) work.”

The ACT team implanted a type of cell called RPE cells made from embryonic stem cells. Those cells are damaged in the two forms of blindness tested in this trial, Stargardt’s macular dystrophy and age-related macular degeneration, the leading cause of blindness in the elderly. Some of the patients have been followed for three years after the cell transplants, which provides the best evidence to date that cells derived from embryonic stem cells can be safe. And some of the patients regained useful levels of vision, which with this small study you still have to consider other possible reasons for the improvement, but it is certainly a positive sign.

CIRM funds a team using a different approach to replacing the RPE cells in these patients and they expect to begin a clinical trial late this year

Stem cells create stronger bone with nanoparticles.   Getting a person’s own stem cells to repair bad breaks in their bones certainly seems more humane than hacking out a piece of healthy bone from some place else on their body and moving it to the damaged area. But our own stem cells often can’t mend anything more than minor breaks. So, a team from Keele University and the University of Nottingham in the U.K. laced magnetic nanoparticles with growth factors that stimulate stem cell growth and used external magnets to hold the particles at the site of injury after they were injected.

It worked nicely in laboratory models as reported in the journal Stem Cells Translational Medicine, and reported on the web site benzinga. Now comes the hard step of proving it is safe to test in humans

Stem cells might end chronic shortage of blood platelets. Blood platelets—a staple of cancer therapy because they get depleted by chemotherapy and radiation—too often are in short supply. They can only set on the shelf for five days after a donation. If we could generate them from stem cells, they could be made on demand, but you’d have to make many different versions to match various peoples’ blood type. The latter has been a bit of a moot point since no one has been able to make clinical grade platelets from stem cells.

plateletsA paper published today by Advanced Cell Technologies may have solved the platelet production hurdle and the immune matching all at once. (ACT is having a good week.) They produced platelets in large quantities from reprogrammed iPS type stem cells without using any of the ingredients that make many iPS cells unusable for human therapy. And before they made the platelets, they deleted the gene in the stem cells responsible for the bulk of immune rejection. So, they may have created a so-called “universal” donor.

They published their method in Stem Cell Reports and Reuters picked up their press release. Let’s see if the claims hold up.

Alzheimer’s in a dish—for the second time. My old colleagues at Harvard got a little more credit than they deserved this week. Numerous outlets, including the Boston Globe, picked up a piece by The New York Times’ Gina Kolata crediting them with creating a model of Alzheimer’s in a lab dish for the first time. This was actually done by CIRM-grantee Lawrence Goldstein at the University of California, San Diego, a couple years ago.

But there were some significant differences in what the teams did do. Goldstein’s lab created iPS type stem cells from skin samples of patients who had a genetic form of the disease. They matured those into nerve cells and did see increased secretion of the two proteins, tau and amyloid-beta, found in the nerves of Alzheimer’s patients. But they did not see those proteins turn into the plaques and tangles thought to wreak havoc in the disease. The Harvard team did, which they attributed, in part, to growing the cells in a 3-dimensional gel that let the nerves grow more like they would normally.

The Harvard team, however, started with embryonic stem cells, matured them into nerves, and then artificially introduced the Alzheimer’s-associated gene. They have already begun using the model system to screen existing drugs for candidates that might be able to clear or prevent the plaques and tangles. But they introduced the gene in such a way the nerve cells over express the disease gene, so it is not certain the model will accurately predict successful therapies in patients.

Don Gibbons

Stem cell stories that caught our eye: fast track marketing in Japan, a 3D cell tour and autism

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.

Event showed great progress, but Japan nipping at our heals. The San Diego Union Tribune’s Brad Fikes seemed to be enjoying covering the Stem Cell Meeting on the Mesa in his own backyard in La Jolla. He stayed for the full two days of the industry Partnering Forum and when we chatted he said he had more good material than he could use. I was certainly willing to second the sentiment of the opening paragraph of the story he wrote:

“More than ever before, stem cell therapies appear poised to transform medicine — potentially curing heart disease, diabetes and paralyzing injuries, among other ailments.”

But the last portion of his piece was a little unsettling. He noted the frequent discussion at the meeting of Japan’s new fast track path for marketing stem cell therapies. The CEO of Athersys, one of the leading companies in the field, announced at the meeting that his company would be taking their lead product to Japan first for marketing, not the U.S.

Turning cell biology into a 3-D game. The ability to track cells has become one of the most important limiting factors in stem cell biology. We need to know where cells go when they are transplanted in the body, but even before that, we have found that the interaction of cells with their environment often determines if stem cell offspring do their jobs and we need to track cells to understand this.

Now a team at Drexel University that includes an expert in computer software and hardware used in gaming has

Researchers at Drexel touring a group of cells using 3D glasses.

Researchers at Drexel touring a group of cells using 3D glasses.

provided the field with an invaluable tool. They can label various cells with distinctive markers and follow their movements. More important they can use an elaborate software program to integrate individual slices of a tissue into a 3D sample that researchers can “tour” while wearing 3D glasses.

Red Orbit quoted Andrew Cohen the leader of the computer development team:

“It’s like Photoshop for cell biologists. The software outlines cells and blood vessels, keeping track of them as they’re dividing and moving around one another. This provides a wealth of information on the patterns of cell shape, motion and division. Visualization of the 3-D microscopy data together with the analysis results is a key step to measure and ultimately understand what drives these cells.”

Cally Templea, a leading expert from the Neural Stem Cell Institute in Rensselaer, NY, was also quoted about the power of this new tool to help stem cell biologists understand how stem cells interact with their environment:

“LEVER 3-D is amazing, it opens new vistas for understanding the stem cell niche.”

Autism linked to stem cell burst (in mice). The accelerated brain growth seen right after birth in many people with autism spectrum disorder has been linked to a burst of nerve stem cell division triggered by inflammation. The study at the University of California, Los Angeles, could explain why inflammation during pregnancy, either due to an autoimmune reaction or an infection, has been shown to be a risk factor for the disorder.

Health Canal posted the press release from the university that quoted the senior author of a paper in the journal Stem Cell Reports, Harley Kornblum:

“We have now shown that one way maternal inflammation could result in larger brains and, ultimately, autistic behavior, is through the activation of the neural stem cells that reside in the brain of all developing and adult mammals.”

The researchers gave pregnant mice a toxin found in bacteria and discovered that it triggered an excess production of nerve stem cells in their pups. This resulted in enlarged brains and behavior associated with autism, such as a reduced interest in interacting with other mice.

Little guy regrowing his head could help us. While a few species have the ability to regrow a severed body part, the tiny Hydractinia—commonly called snail fur—out does the rest in that it can regrow its head. BBC did a nice job of describing work at the University of Galway trying to explain how it accomplishes the feat and putting the work into perspective with other recent research findings.

After harvesting the creatures off the backs of hermit crabs the Galway team isolated embryonic stem cells from them, to which they attributed the ability to regrow something as complex as a head. The snail fur may be unique in that no other adult animal is believed to harbor embryonic stem cells. The researchers hope to use the tiny creature to learn how we might be able to turn on some ancestral regenerative capacity in humans.

Don Gibbons

Meeting designed to bring together investors and researchers seemed to hit pay dirt this year

When I helped plan the first Partnering Forum at the Stem Cell Meeting on the Mesa four years ago, I must admit it felt a bit early for the stated goal of the meeting, which was to bring together academic research teams and early stage biotech companies with big pharmaceutical companies and other investors who could help take the therapies to the patients. The air of the resulting meeting was excitement moderated by caution and a healthy dose of skepticism.

This year’s even that ended yesterday felt very different. First it grew from a couple hundred to more than 700. It followed a period that saw a series of major investments in the field. One speaker noted that in the previous 12 months, $2.5 billion had been invested in cell and gene therapies, double the amount of the prior 12 months. At one panel discussion, a venture capital executive announced that his company was ready to invest in one of our grantees. He had seen them present their research in prior years and their project was not ready then, but it is now.

A panel on regulatory hurdles to advancing cell therapies, including CIRM senior VP Ellen Feigal (second from left) talked about the need for the community to share information.

A panel on regulatory hurdles to advancing cell therapies, including CIRM senior VP Ellen Feigal (second from left) talked about the need for the community to share information.

Many speakers still called for caution, but at a different level. Several companies are expected to report results from Phase 3 clinical trials—the large late stage trials that decide if a therapy is ready for marketing—and they noted that the industry needs good results from some of those trials. A frequent refrain voiced the need for clear data on clinical outcome that makes it easy to show a superior benefit for patients compared to what’s available today.

Our President and CEO Randal Mills led off the second day of the event with a discussion of the restructuring of our grant making process that he refers to as “CIRM 2.0.” His goal is to cut the time from eligibility to submit a grant to the time it is awarded from the current average of 22 months to just 81 days. The concept created an immediate buzz in the room that lasted through lunch three hours later.

But as Randy likes to say, “It is all about the patients.” He noted in his presentation that in his prior position, working on a stem cell therapy for pediatric Graft Versus Host Disease—a horrible deadly complication that strikes half of kids getting bone marrow transplants for cancer—that extra 20 months equals another 750 dying kids.

Everyone here seemed to be in sync on reducing the time to develop therapies. If someone produced a word map of the event, “accelerate” would be large and near the middle as one of the most spoken words.

Don Gibbons

Stem cell stories that caught our eye: heart disease, blindness and replacement teeth

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.

Review looks at approaches to blindness.
The Scientist published a nice lay level overview of various teams’ work to use stem cells to cure blindness. The bulk of the story covers age-related macular degeneration, the most common form of blindness in the elderly, with six approaches discussed and compared including the CIRM-funded California Project to Cure Blindness.

Dennis Clegg, one member of the California project team, was featured in a story posted by his university

The piece smartly includes an overview of the reasons eye diseases make up a disproportionate number of early stem cell trials using stem cells from sources other than bone marrow. Many in the field view it as the perfect target for early therapies where safety will be a main concern. It is a confined space so the cells are less likely to roam; it is small so fewer cells will be needed; and it has reduced immune activity so less likely to reject new cells.

The author describes three approaches to using cells derived from embryonic stem cells, one using iPS-type stem cells, one using fetal-derived nerve stem cells and one using cells from umbilical cord blood. An ophthalmologist from the University of Wisconsin who was not associated with any of the trials offered a fair assessment:

“We’re pushing the boundaries of this technology. And as such, we expect there to be probably more bumps in the road than smooth parts.”


A heart of gold, nanoparticles that is.
Most teams using scaffolds seeded with cells to create patches to strengthen damaged hearts start with animal material to create the scaffold, which can cause immune problems. An Israeli group has developed a way to use a patient’s own fat tissue to create these scaffolds. But that left the remaining problem of getting cells in a scaffold to beat in unison with the native heart. They found that by lacing the scaffold with gold nanoparticles they could create an effective conduction system for the heart’s electrical signals.

A story in ScienceDaily quotes the lead researcher Tal Dvir:

“The result was that the nonimmunogenic hybrid patch contracted nicely due to the nanoparticles, transferring electrical signals much faster and more efficiently than non-modified scaffolds.”

If you read the story parts of it are a little overwrought. The headline, “A Heartbeat away? Hybrid patch could replace transplants,” pushes credibility on two fronts. The first half suggests this therapy is imminent, rather than the reality of years away. Patches could only replace the need for transplants. They could never work as well as a full new heart, but since we only need partial function in our heart to live relatively OK, and they might be safer than a transplant they might replace the need.

Could teeth be first complex organ stem cell success? The Seattle Times did a pretty thorough story about why the tooth might be the first complex organ replaced via stem cells and regenerative medicine. While it is a complex organ with multiple layers, a blood system and a nervous system, it does not have moveable parts and we understand each part better than with other major organs.

The paper starts with a good reminder of just how far dental hygiene has come, with few elderly people needing dentures today—leaving the need for new teeth, suggests the author, to people such as hockey players.

A CIRM-funded team is investigating various ways to build a new tooth.

Even the Tea Party would like this regulation.
We have roughly as many genes as a frog, but are much more complicated. Our higher function evolved in part by making our genes more highly regulated. A CIRM-funded team now reports that this particularly applies to our “jumping genes,” and no that does not have anything to do with jumping frogs.

The work focuses on transposons, bits of our DNA that literally move around, or jump, between our functional genes and change how they are turned on or off. We also have evolved a set of genes to control the jumping genes, and the researchers at the University of California, Santa Cruz, suggest that evolution has been a never ending tug of war between the jumping genes and the genes that are supposed to control them.

HealthCanal ran the university’s press release, which quotes lead researcher Sofie Salama:

“We have basically the same 20,000 protein-coding genes as a frog, yet our genome is much more complicated, with more layers of gene regulation. This study helps explain how that came about.”

Don Gibbons

Seventh annual Stem Cell Awareness Day, Oct. 8, will share some of the reasons behind the hope

When we organized the first Stem Cell Awareness Day in 2008 it was a small affair with events in Australia, Canada and a couple venues in California. It has quickly grown to become a sufficiently grass roots event worldwide that we can’t capture all the activities. But we feature 10 events in the US and six international events at our web site stemcellday.com.

Last year's Stem Cell Day event at the Sanford Consortium in San Diego drew a full house.

Last year’s Stem Cell Day event at the Sanford Consortium in San Diego drew a full house.

One entry in particular is truly international: the opening of a science museum exhibit “Super Cells” in Canada before it embarks on a five-year tour across North America, the United Kingdom, and potentially Europe as well. We wrote about the exhibit that CIRM helped to develop last week.

One event that fully embraces the spirit of the day this year will be at the annual Stem Cell Meeting on the Mesa in La Jolla, California. All the various players in the field, researchers, industry executives and investors come together at this annual gather on the famous La Jolla mesa to foster partnerships that can accelerate the movement of discoveries into therapies for patients. These international leaders will be joined by the public at an event on the second night of the meeting. The featured speaker will be Carl June, a real star of one of the field’s breakthrough therapies: using genes to modify cells to treat cancer and HIV.

In California, CIRM-funded institutions in San Diego, Irvine, Los Angeles, Berkeley and Sacramento will be hosting lab tours, seminars and other events for the public. We will also be matching CIRM grantees with high schools up and down the state to offer guests talks on stem cell science. We expect to reach at least 50 classes and more than a thousand students. Similar efforts are taking place in Toronto, Canada and in New York State.

Many of the activities today and throughout the month—we consider all of October a time to share stem cell knowledge—are focused on the general public. A list of those we are aware of can be found on the Stem Cell Awareness Day website.
If you can’t make one of these events but want to discover more about stem cells, here are a few of our best resources:
stem cell basics
Disease fact sheets
A list of our therapies in development

This year attendees at all the events are likely to hear much more than in previous years about potential therapies that have made it through the pipeline and are now being tested (or close to being tested) in patients. The promise and hope of stem cell science is starting to be backed up by data.

Don Gibbons