Month: January 2015

Stem cell stories that caught our eye: new ways to reprogram, shifting attitudes on tissue donation, and hockey legend’s miracle questioned

/ Don Gibbons / Leave a comment

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 produced from skin. Starting with human skin cells a team at the University of Iowa has created iPS-type stem cells through genetic reprogramming and matured those stem cells into insulin-producing cells that successfully brought blood-sugar levels closer to normal when transplanted in mice.

University of Iowa researchers reprogrammed human skin cells to create iPS cells, which were then differentiated in a stepwise fashion to create insulin-producing cells. When these cells were transplanted into diabetic mice, the cells secreted insulin and reduced the blood sugar levels of the mice to normal or near-normal levels. The image shows the insulin-producing cells (right) and precursor cells (left). [Credit: University of Iowa]

University of Iowa researchers reprogrammed human skin cells to create iPS cells, which were then differentiated in a stepwise fashion to create insulin-producing cells. When these cells were transplanted into diabetic mice, the cells secreted insulin and reduced the blood sugar levels of the mice to normal or near-normal levels. The image shows the insulin-producing cells (right) and precursor cells (left).
[Credit: University of Iowa]

The cells did not completely restore blood-sugar levels to normal, but did point to the possibility of achieving that goal in the future, something the team leader Nicholas Zavazava noted in an article in the Des Moines Register, calling the work an “encouraging first step” toward a potential cure for diabetes.

The Register discussed the possibility of making personalized cells that match the genetics of the patient and avoiding the need for immune suppression. This has long been a goal with iPS cells, but increasingly the research community has turned to looking for options that would avoid immune rejection with donor cells that could be off-the-shelf and less expensive than making new cells for each patient.

Heart cells from reprogramming work in mice. Like several other teams, a group in Japan created beating heart cells from iPS-type stem cells. But they went the additional step of growing them into sheets of heart muscle that when transplanted into mice integrated into the animals own heart and beat to the same rhythm.

The team published the work in Cell Transplantation and the news agency AlianzaNews ran a story noting that it has previously been unclear if these cells would get in sync with the host heart muscle. The result provides hope this could be a route to repair hearts damaged by heart attack.

Patient attitudes on donating tissue. A University of Michigan study suggests most folks don’t care how you use body tissue they donate for research if you ask them about research generically. But their attitudes change when you ask about specific research, with positive responses increasing for only one type of research: stem cell research.

On the generic question, 69 percent said go for it, but when you mentioned the possibility of abortion research more than half said no and if told the cells might lead to commercial products 45 percent said nix. The team published their work in the Journal of the American Medical Association and HealthCanal picked up the university’s press release that quoted the lead researcher, Tom Tomlinson, on why paying attention to donor preference is so critical:

“Biobanks are becoming more and more important to health research, so it’s important to understand these concerns and how transparent these facilities need to be in the research they support.”

CIRM has begun building a bank of iPS-type stem cells made from tissue donated by people with one of 11 diseases. We went through a very detailed process to develop uniform informed consent forms to make sure the donors for our cell bank knew exactly how their cells could be used. Read more about the consent process here.

Mainstream media start to question hockey legend’s miracle. Finally some healthy skepticism has arrived. Hockey legend Gordie Howe’s recovery from a pair of strokes just before the holidays was treated by the general media as a true Christmas miracle. The scientific press tried to layer the coverage with some questions of what we don’t know about his case but not the mainstream media. The one exception I saw was Brad Fikes in the San Diego Union Tribune who had to rely on a couple of scientists who were openly speaking out at the time. We wrote about their concerns then as well.

Now two major outlets have raised questions in long pieces back-to-back yesterday and this morning. The Star in hockey-crazed Canada wrote the first piece and New York Magazine wrote today’s. Both raise serious questions about whether stem cells could have been the cause of Howe’s recovery and are valuable additions to the coverage.

Getting the right tools for the right job

/ Kevin McCormack / 1 Comment

Imagine a device that sits outside the body and works like a form of dialysis for a damaged liver, filtering out the toxins and giving the liver a chance to regenerate, and the patient a chance to avoid the need for a transplant.

Or imagine a method of enhancing the number of stem cells we can harvest or generate from umbilical cord blood, enabling us to use those stem cells and offer life-saving bone marrow transplants to all the patients who don’t have a matched donor.

Well, you may not have to imagine for too long. Yesterday, our governing Board approved almost $30 million in funding for our Tools and Technology Awards and two of the successful applications are for researchers hoping to turn those two ideas into reality.

The Tools n Tech awards may not have the glamor or cache of the big money awards that are developing treatments heading towards clinical trials, but they are nonetheless an essential part of what we do.

As our Board Chair Jonathan Thomas said in a news release they focus on developing new approaches or creating new ways of overcoming some of the biggest obstacles in stem cell research.

“Sometimes even the most promising therapy can be derailed by a tiny problem. These awards are designed to help find ways to overcome those problems, to bridge the gaps in our knowledge and ensure that the best research is able to keep progressing and move out of the lab and into clinical trials in patients.”

Altogether 20 awards were funded for a wide variety of different ideas and projects. Some focus on improving our ability to manufacture the kinds of cells we need for transplanting into patients. Another one plans to use a new class of genetic engineering tools to re-engineer the kind of stem cells found in bone marrow, making them resistant to HIV/AIDS. They also hope this method could ultimately be used to directly target the stem cells while they are inside the body, rather than taking the cells out and performing the same procedure in a lab and later transplanting them back.

Dr. Kent Leach, UC Davis School of Engineering

Dr. Kent Leach, UC Davis School of Engineering

One of the winners was Dr. Kent Leach from the University of California, Davis School of Engineering. He’s looking to make a new kind of imaging probe, one that uses light and sound to measure the strength and durability of bone and cartilage created by stem cells. This could eliminate the need for biopsies to make the same measurements, which is good news for patients and might also help reduce healthcare costs.

We featured Dr. Leach in one of our Spotlight videos where he talks about using stem cells to help repair broken bones that no longer respond to traditional methods.

Extending the Lease: Stanford Scientists Turn Back Clock on Aging Cells

/ cirmweb / Leave a comment

In the end, all living things—even the cells in our bodies—must die. But what if we could delay the inevitable, even just for a bit? What new scientific advances could come as a result?

Stanford scientists have found a way to temporarily extend the life of an aging cell.

Stanford scientists have found a way to temporarily extend the life of an aging cell.

In research published this week in the FASEB Journal, scientists at the Stanford University School of Medicine have devised a new method that gives aging DNA a molecular facelift.

The procedure, developed by Stanford Stem Cell Scientist Helen Blau and her team at the Baxter Laboratory for Stem Cell Biology, physically lengthens the telomeres—the caps on the ends of chromosomes that protect the cell from the effects of aging.

When born, all cells contain chromosomes capped with telomeres. But during each round of cell division, those telomeres shrink. Eventually, the telomeres shorten to such an extent that the chromosomes can no longer replicate at the rate they once could. For the cell, this is the beginning of the end.

The link between telomeres and cellular aging has been an intense focus in recent years, including the subject of the 2009 Nobel Prize in Physiology or Medicine. Extending the lifespan of cells by preventing—or reversing— the shortening of telomeres can not only boost cell division during laboratory studies, but can also lead to new therapeutic strategies to treat age-related diseases.

“Now we have found a way to lengthen human telomeres… turning back the internal clock in these cells by the equivalent of many years of human life,” explained Blau in a press release. “This greatly increases the number of cells available for studies such as drug testing or disease modeling.”

The method Blau and her team describe involves the use of a modified bit of RNA that boosts the production of the protein telomerase. Telomerase is normally present in high levels in stem cells, but drops off once the cells mature. Blau’s modified RNA gives the aging cells a shot of telomerase, after which they begin behaving like cells half their age. But only for about 48 hours, after which they begin to degrade again.

The temporary nature of this change, say the researchers, offers significant advantages. On the biological level, it means that the treated cells won’t begin dividing out of control indefinitely, minimizing the risk of tumor formation. The study’s first author John Ramunas offers up some additional pluses to their method:

“Existing methods of extending telomeres act slowly, whereas our method acts over just a few days to reverse telomere shortening that occurs over more than a decade of normal aging. This suggests that a treatment using our method could be brief and infrequent.”

Indeed, the genetic disease Duchenne muscular dystrophy is in part characterized by abnormally short telomeres. Blau reasons that their discovery could lead to better treatments for this disease. Their immediate future steps involve testing their method in a variety of cell types. Said Blau:

“We’re working to understand more about the differences among cell types, and how we can overcome those differences to allow this approach to be more universally successful.”

Hear more about stem cells and muscular dystrophy in our recent Spotlight on Disease featuring Helen Blau:

Our Tainted Food Supply: Its Lasting Effects on Stem Cells May Explain Declines in Sperm Counts

/ Todd Dubnicoff / Leave a comment

Spermatozoons, floating to ovuleIn the science fiction film, Children of Men, humans in the year 2027 face extinction due to decades of infertility. This premise doesn’t seem all that far-fetched when you consider studies in the U.S., Japan, and Europe over the past two decades that point to declining sperm counts. A 2013 study, for instance, that followed 26,000 French men for 17 years reported a 32% drop in sperm counts. And a study of 5000 Danish men with a median age of 19 found 40% had sperm counts corresponding to infertility or decreased fertility.

So what’s going on here? One line of evidence blames exposure to chemicals that leach into our food and water supply. A possible culprit is the much-despised Bisphenol-A, or BPA, a man-made chemical found in plastic bottles, the inner linings of canned food and even receipt paper used at your local grocery store. BPA is known as a hormone disruptor because it interferes with normal hormone activity in the body by mimicking the female hormone estrogen. Lab animals exposed to low levels of BPA have shown increased incidence of certain cancers, neurological problems, diabetes, obesity, female reproduction problems and, yes, decreased sperm counts.

BPA_shutterstock_243369064Data published last week in PLOS Genetics appears to have pinpointed the link between BPA and decreased sperm counts: stem cells. Specifically the so-called spermatogonial stem cells that give rise to sperm. In the Washington State University study, the research team gave newborn male mice daily oral doses of BPA for about two weeks. The chemical exposure negatively affected this spermatogonial stem cell population by disrupting the processing of the cells’ DNA and, in turn, the development of fully mature sperm. The team got similar results replacing BPA with synthetic estrogen found in birth control pills. This form of estrogen is also known to contaminate our water supply even after sewage treatment.

A surprising and even scary twist to these results is that the brief exposure of BPA or estrogen in the newborn male mice permanently changed their stem cells. The team confirmed this observation by transplanting the spermatogonial stem cells from BPA-exposed mice into the testes of mice that never received BPA. In this case, these mice still exhibited reduced sperm production. As senior author Nancy Hunt points out in an interview with Scientific American, the exposure to these chemicals:

“is not simply affecting sperm being produced now, but impacting the stem cell population, and that will affect sperm produced throughout the lifetime.”

It’s remains debatable whether the detectable BPA or estrogen levels in our food and water supply is high enough to actually cause health problems in humans. In 2013 the Food and Drug Administration (FDA) downplayed possible worries on its website:

“Is BPA safe? Yes. Based on FDA’s ongoing safety review of scientific evidence, the available information continues to support the safety of BPA for the currently approved uses in food containers and packaging.”

Still, this recent study and others like it certainly warrant further investigation. University of Missouri scientist Frederick vom Saal, who was not part of the study, put it this way in his interview with Scientific American:

“It’s important in future studies to see if the stem cell changes from exposure are passed to future generations… Since most people are consistently exposed to BPA and other estrogenic compounds, each generation could have it a bit worse.”

Scientists Develop Colorful Cell-Imaging Technique

/ cirmweb / Leave a comment

Proteins are the helmsmen of the cell. They drive the essential processes that keep cells alive, keep them healthy and keep them functioning. And in recent years scientists have discovered that proteins rarely act alone.

In fact, so-called ‘protein-protein interactions’ are now known to drive the vast majority of cellular functions. But figuring out exactly how they do so has proven difficult.

Luckily, scientists now have a way to see these interactions—in a dazzling array of Technicolor.

As described in today’s issue of Nature Methods, Robert Campbell and his team at the University of Alberta have announced a new way to visualize protein-protein interactions, by converting these interactions into changes in color. This technique could be employed across a variety of disciplines, helping scientists understand normal processes in the cell—and observe the molecular changes that occur when those processes go awry.

“With this development,” explained Campbell in a news release, “we can immediately image activity happening at the cellular level, offering an alternative to existing methods for detecting and imaging of protein-protein interactions in live cells.”

Called FPX, Campbell’s method links a change in a protein-protein interaction to a color. As seen in the video below, every time the interaction changes, a color change—from red to green, and back to red again—is visible.

The FPX method is based on previously published work by Campbell and others, which found that green and red fluorescent proteins could both be inserted into a single cell so that the protein could be red or green—but not both at the same time. So, the team was able to construct biosensors that changed color in response to changes in protein-protein interactions.

In this study, the researchers have essentially given scientists a powerful tool to help them understand how even the smallest molecular changes can lead to significant changes in the health of the cell.

According to Campbell:

“It will be immediately relevant to many areas of fundamental cell biology research and practical applications such as drug discovery. Ultimately, it will help researchers achieve breakthroughs in a wide variety of areas in the life sciences, such as neuroscience, diabetes and cancer.”

Stem cell stories that caught our eye: Heart self-repair, MS therapy and genetic screening

/ Don Gibbons / Leave a comment

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.

Uncovering mystery of heart self-repair. We have often written about work that tries to get the body’s self-healing mechanisms to do a better job. This is particularly desirable but difficult in heart injury. A CIRM-funded team as Children’s Hospital Los Angeles found some clues to achieving this goal by investigating critters good at it. Neonatal mice have an amazing capacity to repair heart damage for about the first seven days of their life.

A young mouse heart with resting heart muscle cells (red) and proliferating muscle cells (green)

A young mouse heart with resting heart muscle cells (red) and proliferating muscle cells (green)

The team looked at what genetic and molecular systems were active during the period of repair and not active at other times. Senior author of the study, Ellen Lien, described the importance of what they are finding in a press release picked up by ScienceCodex:

“Using models such as zebrafish and neonatal mice that regenerate their hearts naturally, we can begin to identify important molecules that enhance heart repair.”

Good news on MS needed many caveats. Some good news on using stem cell transplants for Multiple Sclerosis published in the Journal of the American Medical Association this week sparked a flurry of news reports. But most of those stories lacked the caveats the study required and generated several calls to our office from desperate patients wanting to try the therapy. HealthDay did a good job of pointing out the hope and the limitations of the therapy and of the clinical trial itself.

Only half of the patients responded, which is still good for what can be such an intractable disease. But, only one subset of patients showed the benefit; ones earlier in the course of the disease with the form known as relapsing-remitting MS. None of the later stage patients responded, which makes some sense because if the transplant is altering the immune system, it would have the most impact when the patient’s immune cells are most actively attacking their nerves.

A personal tale of using genetic screening of embryos. Over the past couple years researchers’ need for new embryonic stem cell lines has declined. As a result, many of the new cell lines registered with the National Institutes of Health in the past year have been ones carrying specific genetic disease traits that have been screened out of consideration by couples using pre-implant genetic diagnosis (PGD) for family planning at in vitro fertilization clinics.

While we have written about this conceptually a feature story posted by the University of Michigan and picked up by ScienceDaily makes it very real through a family’s personal story. A devastating nerve disease called ALD runs in the prospective mother’s family so they decided to use PGD to avoid having a child with the disease, but they took it one step further. They donated the left over embryos that carried the genetic flaw to the university for research. Now they are about to celebrate the first birthday of a healthy son and the researchers have a valuable research tool as one stem cell scientist at the University, Gary Smith, explained:

“Disease-specific human embryonic stem cells are the gold standard for research —the purest pathway to understanding disease establishment and progression, and to discovering ways to prevent or alleviate pain and suffering caused by these diseases.”

Scientists Send Rodents to Space; Test New Therapy to Prevent Bone Loss

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In just a few months, 40 very special rodents will embark upon the journey of a lifetime.

shutterstock_200932226

Today UCLA scientists are announcing the start of a project that will test a new therapy that has the potential to slow, halt or even reverse bone loss due to disease or injury.

With grant funding from the Center for the Advancement of Science in Space (CASIS), a team of stem cell scientists led by UCLA professor of orthopedic surgery Chia Soo will send 40 rodents to the International Space Station (ISS). Living under microgravity conditions for two months, these rodents will begin to undergo bone loss—thus closely mimicking the conditions of bone loss, known as osteoporosis, seen in humans back on Earth.

At that point, the rodents will be injected with a molecule called NELL-1. Discovered by Soo’s UCLA colleague Kang Ting, this molecule has been shown in early tests to spur bone growth. In this new set of experiments on the ISS, the researchers hope to test the ability of NELL-1 to spur bone growth in the rodents.

The team is optimistic that NELL-1 could really be key to transforming how doctors treat bone loss. Said Ting in a news release:

“NELL-1 holds tremendous hope, not only for preventing bone loss but one day even restoring healthy bone. For patients who are bed-bound and suffering from bone loss, it could be life-changing.”

“Besides testing the limits of NELL-1’s robust bone-producing efforts, this mission will provide new insights about bone biology and could uncover important clues for curing diseases such as osteoporosis,” added Ben Wu, a UCLA bioengineer responsible for initially modifying NELL-1 to make it useful for treating bone loss.

The UCLA team will oversee ground operations while the experiments will be performed by NASA scientists on the ISS and coordinated by CASIS.

These experiments are important not only for developing new therapies to treat gradual bone loss, such as osteoporosis, which normally affects the elderly, but also those who have bone loss due to trauma or injury—including bone loss due to extended microgravity conditions, a persistent problem for astronauts living on the ISS. Said Soo:

“This research has enormous translational application for astronauts in space flight and for patients on Earth who have osteoporosis or other bone-loss problems from disease, illness or trauma.”

What…exactly…do you do? How 12 year olds helped me learn how to talk about science

/ Kevin McCormack / 1 Comment
Jackie Ward in her lab at UC San Diego

Jackie Ward in her lab at UC San Diego

Jackie Ward is a graduate student at the University of California, San Diego (UCSD), and received a training grant from CIRM while studying for her PhD. At UCSD Jackie uses stem cells as a model to study rare neurodegenerative diseases in the lab of Albert La Spada. Her work as a PhD student focuses on a rare form of inherited neurodegeneration called spinocerebellar ataxia. From time to time Jackie shares her experiences with us. Here’s her latest.

One of the many questions I get over my annual trek home during the holidays is “What…exactly…do you do?” This is usually couched somewhere between “have you learned to surf yet?” and “how’s the weather?” In the past, I preferred to talk about my surfing skills (very minimal) and the sunshine (always amazing, thanks San Diego), more than what I do every day. It’s amazing how this seemingly innocuous question can be the most difficult to answer. Because we’re used to presenting our work in lecture formats or lengthy scientific papers, summing it up in three sentences of non-jargon can be difficult. A similar thought was outlined recently at UCSD, by the actor and science advocate Alan Alda. The title of his presentation, “Getting the Public Past a Blind Date with Science,” highlighted the uncomfortable feelings many people have towards science. Like any relationship, sustained communication and trust is necessary for success. Unfortunately, on many scientific issues, that relationship has suffered. As a PhD student, I am constantly surrounded by my peers—other scientists who know exactly what I mean when I use terms like “reprogramming” or “retinal photoreceptor.” While these scientist-to-scientist conversations are vital to our work, we often forget that it is equally, or perhaps more, important to have conversations with people who have no idea what we do. As any CIRM- or NIH-funded lab is well aware, a significant portion of our funding comes from taxpayer dollars. It’s these “investors” to whom we ultimately report back. This conversation is challenging. Not only do we have to change our language, we have to remember what it was like to not know everything we do now. The best practice I’ve gotten in this regard is talking to kids. Seventh graders seem to be less afraid to ask you questions or call you out on something that doesn’t make sense to them. (Now that I think about it, it might be beneficial to include some 13-year-olds on our grant review panels.) My graduate program allows students to fulfill their teaching requirement by doing science outreach activities. I chose to do this with the Salk Institute’s mobile science lab, where real scientists are connected to local middle schools to discuss their jobs and lead hands-on science labs. I didn’t realize how valuable this experience was until it started to become easier for me to answer the “what do you do” question. I changed the words I use. I replaced the word “reprogram” with “rewind” and “retinal photoreceptor” with “eye cell.” Unexpectedly, I think this practice helped me become a better communicator when I talk to other scientists now too. I try not to assume a certain level of knowledge with anybody. While I still love talking about pretending to surf and gloating about the weather, I’ve become more fond of the “what do you do” question. I hope to only improve with time. It’ll be my small contribution for getting science to that second date.

UC Davis Surgeons Begin Clinical Trial that Tests New Way to Deliver Stem Cells; Heal Bone Fractures

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Each year, approximately 8.9 million people worldwide will suffer a bone fracture. Many of these fractures heal with the help of traditional methods, but for some, the road to recovery is far more difficult.

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After exhausting traditional treatments—such as surgically implanted pins or plates, bed rest and injections to spur bone growth—these patients can undergo a special type of stem cell transplant that directs stem cells extracted from the bone marrow to the fracture site to speed healing.

This procedure has its drawbacks, however. For example, the act of extracting cells from one’s own bone marrow and then injecting them into the fracture site requires two very painful surgical procedures: one to extract the cells, and another to implant them. Recovery times for each procedure, especially in older patients, can be significant.

Enter a team of surgeons at UC Davis. Who last week announced a ‘proof-of-concept’ clinical trial to test a device that can extract and isolate stem cells far more efficiently than before—and allow surgeons to implant the cells into the fracture in just a single surgery.

As described in HealthCanal, he procedure makes use of a reamer-irrigator-aspirator system, or RIA, that normally processes wastewater during bone drilling surgery. As its name implies, this wastewater was thought to be useless. But recent research has revealed that it is chock-full of stem cells.

The problem was that the stem cells were so diluted within the wastewater that they couldn’t be used. Luckily, a device recently developed by Sacramento-based SynGen, Inc., was able to quickly and efficiently extract the cells in high-enough concentrations to then be implanted into the patient. Instead of having to undergo two procedures—the patient now only has to undergo one.

“The device’s small size and rapid capabilities allow autologous stem cell transplantation to take place during a single operation in the operation room rather than requiring two procedures separated over a period of weeks,” said UC Davis surgeon Mark Lee, who is leading the clinical trial. “This is a dramatic difference that promises to make a real impact on healing and patient recovery.”

Hear more from Lee about how stem cells can be used to heal bone fractures in our 2012 Spotlight on Disease.