Stem cell stories that caught our eye: two new approaches to treating diabetes and a video on why this work excites

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.

Insulin producing cells avoid immune rejection. The phrase, there is more than one way to skin a cat often applies to the science of trying to develop therapies. A CIRM-funded team at the company Viacyte is working to cure diabetes and has developed a cell line that is a middleman, or precursor cell, part way between a stem cell and a fully mature insulin-producing cell. When transplanted into animal patients it has been shown to mature into the needed cells and correct the faulty sugar levels caused by the disease.

But, the company could not just transplant those cells into patients whose own insulin-producing cells had been destroyed by their immune system without protecting them from that immune attack. In a human trial we are funding that began in September the Viacyte team protects the cells inside a small porous pouch placed under the skin.

Insulin-producing cells shown in green surviving after transplant because of the new procedure.

Insulin-producing cells shown in green surviving after transplant because of the new procedure.

Now they have reported in Cell Stem Cell work done with researchers at the University of California, San Francisco that shows that a drug-like pretreatment can alter the animal’s immune response and let the new cells survive without the protective pouch. Those cells, called PEC-01, were protected by agents that blocked a very specific part of the immune system that causes immune rejection—a much gentler treatment than the immune suppression used for organ transplants.

The San Diego Union Tribune did a nice job of putting the two approaches into perspective, and Reuters picked up the company’s press release that quotes the senior UCSF researcher Jeffrey Bluestone:

“The demonstration that these new immunotherapies block specific pathways and immune cells that are responsible for attacking pancreatic islet cells and prevent the rejection of implanted PEC-01 cells is an exciting finding that could lead to advances in the way we treat diabetes and other diseases.”

Stem cell work a runner up for discovery of the year. Each year the journal Science names a discovery of the year and nine runners up. This year the Mars rover took top honors but a Harvard team scored a runner up slot for its work creating mature insulin producing cells from stem cells in the lab. Many labs had failed to accomplish this feat over the past several years.

I agree this is a big deal, but many researchers in the field believe that the best place to mature stem cells into the desired tissue is in the patient where they can take cues from the body that are much more complex than what we can recreate in the lab. The Viacyte team cited above uses the in-the-body approach and is already testing the therapy in patients.

Toward the end of the original Harvard press release and at the end of the notice in Science, the authors note that before the work can be used in patients they need to overcome the patient’s immune reaction—something the most recent Viacyte discovery might be able to help achieve.

Clue found for how stem cells make decisions.
Many a researcher has used the Bizarro cartoon labeled “Stem Cell Parental Advice” with the thought balloon “You are a stem cell you can become anything you want when you grow up.” Researchers have found that ability to be a double-edged sword. Since stem cells can become anything it is often hard to direct them efficiently down a particular desired path.

Now a Danish team from the University of Copenhagen has documented in Cell Reports a way to block all the various maturation paths and keep the stem cells in a stem cell state. This could be a first step to being able to consistently direct them down one preferred path. Science Codex picked up the university’s press release, which quoted a member of the research team, Joshua Brickman on why this could be valuable:

“If you block all the choices they can make, they stay in the stem cell state. If you only allow them one door to exit from the stem cell state, you should be able to make particular cell types more efficiently. So if you only leave one door open then it’s the path of least resistance and when you give them a push they really go.”

Video captures the excitement of stem cell researchers. Stanford’s research blog Scope produced a fun end-of-the-year piece that includes a video of researcher Margaret Fuller describing why she is so excited to work in this field. One example she cites came from a recent report about using stem cells to help repair lost muscle in wounded soldiers returning from Afghanistan. I’ll let you watch the video to see why she said “It gives me chills just thinking about it.”

Stem cell stories that caught our eye: good fat vs. bad fat, the black box of cell reprogramming and Parkinson’s

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

One day a pill might turn bad fat into good fat. For a few years now several research teams have linked white fat to the bad health effects of fat and brown fat to more positive metabolism and to being leaner. Now, a team at the Harvard Stem Cell Institute has used stem cells in the laboratory as a screening tool to look for drugs that could cause the bad fat to turn into the good fat.

Brown fat derived from stem cells. Image courtesy of Harvard

Brown fat derived from stem cells. Image courtesy of Harvard

They have found two molecules that can prevent fat stem cells from becoming mature white fat and instead direct them to become brown fat. But those two molecules used as pills would likely have too many unintended side effects to become a treatment that would likely need to be taken long-term. So, despite some overblown headlines about a “pill to replace a treadmill,” don’t count on it anytime soon.

That treadmill line came from a story in the Harvard Gazette, but to the school’s credit they did follow-up with the needed caveats:

“The path from these findings to a safe and effective medication may not be easy, and the findings will have to be replicated by other research groups, as well as refined, before they could lead to a clinical treatment.”

Opening up the black box of reprogramming cells. Researchers around the world have been turning adult cells into embryonic-like stem cells ever since Shinya Yamanaka’s Nobel-prize winning work showing it was possible more than six years ago. But no one really knew how it works. And that lack of understanding has made it quite difficult to improve on the poor efficiency and mixed-results of the process.

This led 30 senior scientists at eight institutions around the world to launch a project in 2010 to create an extremely detailed map of all the switching on and off of genes over time during the weeks it takes to reprogram adult cells to become “pluripotent” stem cells. The effort, called Project Grandiose, reported its results this week in a series of three papers in the journal Nature Communications. The name comes in part from the massive size of the data sets involved. Files could not be sent electronically. The teams were shipping memory storage devices around the world by courier. The leader of the project, Andras Nagy of Mount Sinai Hospital in Toronto described the project in a review of the field in Nature:

“It was the first high-resolution analysis of change in cell state over time. I’m not shy about saying grandiose.”

That journal review provides the best history of reprogramming that I have read and it is written on a level that a lay science hobbyist could understand. It gives a good explanation for one of the surprise findings from Project Grandiose that got a little over-played in some coverage. That was discovery of a new type of pluripotent stem cell called F Class, not referring to Mercedes car lines, but rather the fact that the cell clusters in a lab dish look fuzzy. The process that creates them in the lab seems to be more efficient than traditional reprogramming.

The critical output of the international project is more practical. Researchers around the world now have myriad new ways to think about improving the production of reprogrammed stem cells. Ken Zaret of the University of Pennsylvania, and a long time toiler in the field told the author of the Nature review this work opens up options for more reliable sources of cells to be used in human medicine:

“The motivation of my research is to treat patients. Anything that helps push iPS cells into the clinic excites me.”

Stem cells from inside the nose treat Parkinson’s in rats. A type of stem cell found in tissue that in humans would be thrown out after sinus surgery was retrieved from rats and then injected into the parts of their brains that do not function properly in Parkinson’s disease (PD). After 12 weeks the cells had migrated to where they were needed and matured into the type of nerve cell needed to cure PD and improved the function of the animals.

The cells, called inferior turbinate stem cells, could be a way to use a patient’s own stem cells as therapy for PD and avoid issues of immune rejection of donor cells, which may or may not be an issue in the brain, but this would remove a layer of risk. The work by a team at the University of Bielefeld and Dresden University of Technology in Germany was published in the journal Stem Cells Translational Medicine and the Houston Chronicle picked up the journal’s press release.

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

Stem Cell Stories that Caught our Eye: Skin Cells to Brain Cells in One Fell Swoop, #WeAreResearch Goes Viral, and Genes Helps Stem Cells Fight Disease

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

Building a Better Brain Cell. Thanks to advances in stem cell biology, scientists have found ways to turn adult cells, such as skin cells, back into cells that closely resemble embryonic stem cells. They can then coax them into becoming virtually any cell in the body.

But scientists have more recently begun to devise ways to change cells from one type into another without first having to go back to a stem cell-like state. And now, a team from Washington University in St. Louis has done exactly that.

As reported this week in New Scientist, researcher Andrew Yoo and his team used microRNAs—a type of ‘signaling molecule’—to reprogram adult human skin cells into medium spiny neurons(MSNs), the type of brain cell involved in the deadly neurodegenerative condition, Huntington’s disease.

“Within four weeks the skin cells had changed into MSNs. When put into the brains of mice, the cells survived for at least six months and made connections with the native tissue,” explained New Scientist’s Clare Wilson.

This process, called ‘transdifferentiation,’ has the potential to serve as a faster, potentially safer alternative to creating stem cells.

#WeAreResearch Puts a Face on Science. The latest research breakthroughs often focus on the science itself, and deservedly so. But exactly who performed that research, the close-knit team who spent many hours at the lab bench and together worked to solve a key scientific problem, can sometimes get lost in the shuffle.

#WeAreResearch submission from The Thomson Lab at the University of California, San Francisco. This lab uses optogenetics, and RNAseq to probe cell fate decisions.

#WeAreResearch submission from The Thomson Lab at the University of California, San Francisco. This lab uses optogenetics, and RNAseq to probe cell fate decisions.

Enter #WeAreResearch, a new campaign led by the American Society for Cell Biology (ASCB) that seeks to show off science’s more ‘human side.’

Many California-based stem cell teams have participated—including CIRM grantee Larry Goldstein and his lab!

Check out the entire collection of submissions and, if you’re a member of a lab, submit your own. Prizes await the best submissions—so now’s your chance to get creative.

New Genes Help Stem Cells Fight Infection. Finally, UCLA scientists have discovered how stem cells ‘team up’ with a newly discovered set of genes in order to stave off infection.

Reporting in the latest issue of the journal Current Biology, and summarized in a UCLA news release, Julian Martinez-Agosto and his team describe how two genes—adorably named Yorkie and Scalloped—set in motion a series of events, a molecular Rube Goldberg device, that transforms stem cells into a type of immune system cell.

Importantly, the team found that without these genes, the wrong kind of cell gets made—meaning that these genes play a central role in the body’s healthy immune response.

Mapping out the complex signaling patterns that exist between genes and cells is crucial as researchers try and find ways to, in this case, improve the body’s immune response by manipulating them.

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.

shutterstock_132771389

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: 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

Stem cell stories that caught our eye: heart disease, premature infants and incontinence

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.

Decoding heart health and genetics in Asians. A study from CIRM grantee Joseph Wu at Stanford may point the way to using stem cells to solve problems caused by too many drugs being tested predominantly on white males. Ethnic variations to drug response too often get ignored in current clinical trials.

The Stanford team has used iPS type stem cells to create a disease-in-a-dish model of a genetic mutation that effects 500 million people, but mostly East Asians. The mutation disables the metabolic protein called ALDH2 and results in increased risk of heart disease and increases the risk of death after a heart attack. By growing heart muscle from stem cells made from the skin of patients with the mutation his team found that the defect alters the way the heart cells react to stress.

Wu suggests that drug companies one day may keep banks of iPS cells from various ethnic groups to see how their responses to drugs differ. Science Daily ran the university’s press release.

Stem cells may treat gut disease in premies.
A laundry list of medical challenges confronts premature babies, but few are as deadly as the intestinal disease that goes by the name NEC, or necrotizing enterocolitis. It strikes with no notice and can kill within hours.

140925100256-largeA team at the University of Ohio reports they have developed what may be a two-pronged attack on the disease. First, they found a biomarker that can predict which infants might develop NEC, and second they have tested stem cells for treating the intestinal damage done by the disease. In an animal model they found that a type of stem cell found in bone marrow, mesenchymal stem cells, can reduce the inflammation that causes the damage and that neural stem cells can repair the nerve connections disrupted by the inflammation.

While this explanation sounds straight forward, getting to that potential intervention was anything but a simple path. The university wrote an extensive feature detailing the many years and many steps the research team took to unravel this who-done-it that involves the gut’s extensive “brain” and immune system. Science Daily picked up the piece.

We recently posted a video about a project we fund using stem cells to develop a treatment for irritable bowel disease.

Fat stem cells tested in incontinence. For far too many older women laughing and coughing can lead to embarrassing bladder leaks. Several groups are working with various types of stem cells to try to strengthen the urinary sphincter and help patients lead a more normal life. A team at Cleveland Clinic now reports some positive results using the most easily accessed form of stem cells, those in fat.

They harvested patients’ own fat stems cells, grew them in the lab for three weeks and then mixed them with a collagen gel from cows to hold them in place before injecting them into the sphincter. Three of five patients passed “the cough test” after one year. Good results, but clearly more work needs to be done to yield more uniform results. Stem Cells Translational Medicine published the research and issued this press release.

Some researcher suspect starting with an earlier stage, more versatile stem cell might yield better results. One of our grantees is developing cells to treat incontinence starting with reprogrammed iPS type stem cells.

New course looks at where fact and fiction overlap. I am a big fan of almost any effort to blend science and the arts. A professor at the University of Southern California seems to agree. CIRM grantee Gage Crump will be teaching a course next spring about science fiction and stem cells.

The university says the course, Stem Cells: Fact and Fiction, will range from babies born with three biological parents to regrown body parts. The course will explore the current state of stem cell biology as it closes the gap between reality and the sci fi visions of authors such as Margaret Atwood and Philip K. Dick. Crump describes it as:

“a mad scientist type of course, where we go through some real science but also [think] about what’s the future of science.”

Don Gibbons