Ten at ten at the stem cell agency: sharing the good news about progress from the bench to the bedside

Ten years ago this month the voters of California overwhelmingly approved Proposition 71, creating the state’s stem cell agency, the California Institute for Regenerative Medicine, and providing $3 billion to fund stem cell research in California.

That money has helped make California a global leader in stem cell research and led to ten clinical trials that the stem cell agency is funding this year alone. Those include trials in heart disease, cancer, leukemia, diabetes, blindness, HIV/AIDS and sickle cell disease.

To hear how that work has had an impact on the lives of patients we are holding a media briefing to look at the tremendous progress that has been made, and to hear what the future holds.

When: Thursday, November 20th at 11am

Where: Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at the University of Southern California, 1425 San Pablo Street, Los Angeles, CA 90033

Who: Hear from patients who have benefited from stem cell therapies, the researchers who have done the work, and the key figures in the drive to make California the global leader in stem cell research

To listen in to the event by phone:

Call in: 866.528.2256  Participant code: 1594399

For more information contact: Kevin McCormack, Communications Director, CIRM kmccormack@cirm.ca.gov

Cell: 415-361-2903

Hands-on science turns kids heads

Making science fun. That was the goal of the Discovery Days event on Saturday in San Francisco, part of the Bay Area Science Festival. If numbers alone are any measure of success they certainly met their goal. The place was packed. But it was more than just the size of the crowd that demonstrated how successful the event was; it was also the makeup and enthusiasm of those there.

Using Play-Doh to explain the wonders of stem cells

Using Play-Doh to explain the wonders of stem cells

For five hours on a beautiful, sunny Saturday – when they could have gone anywhere and done anything – tens of thousands of people, parents and children, chose to come to Discovery Days and immerse themselves in science. And they clearly loved it.

There were more than 150 exhibits to choose from with a wide variety of topics to learn about – everything from climate change and exploring outer space to life in the ocean and everything in between.

In just the small section where the stem cell agency had its booth there were exhibits on DNA and genetics, the power of imagination, and a program designed to encourage more young women to pursue careers in engineering and orthopedics.

Each one chose a different way to engage the crowd, some used fancy high tech tools, others chose more basic approaches. At our booth we used Play-Doh to draw children to us where they could learn about cellular development. It’s always fun to see their eyes widen in amazement when you show them how we all began: as a single, solitary cell. And how that single cell quickly divides into many, eventually making up all the different types of cells that make us human.

The stem cell agency booth at Discovery Days at AT&T Park

The stem cell agency booth at Discovery Days at AT&T Park

The enthusiasm by kids and parents alike was infectious—children racing from one booth to the next, eager to see what each one had in store. Of course the fact that some booths wowed the parents as well as the kids didn’t hurt—but the bottom line was the science and the scientists, showing that it could be fun and fascinating and engaging. While not many parents got into the Play-Doh themselves, they spent considerable time talking with us about the progress in stem cell science.

When you look around and see so many children wearing big goggles, pretending to be scientists, it’s not hard to think of them years later, wearing those same goggles and no longer pretending but actually working as researchers—truly making the world a better place.

And ultimately that was the goal of the event, helping the kids find “something that will unleash their inner scientist.”

Discovery Days; bringing new life to the life sciences

Here are three words you don’t often see strung together: free, science, extravaganza. Yet that’s how Saturday’s Discovery Days at AT&T Park in San Francisco (home of the newly crowned baseball world champion Giants) is being described.

Robots on the rampage at last year's Discovery Days science fair

Robots on the rampage at last year’s Discovery Days science fair

The event truly is a celebration of science. It features more than 150 exhibits on everything from stem cells (that’s us) to rockets and robots and learning how your body and your brain work. It lets you learn about the world through interactive displays, games and experiments that engage and entertain.

Discovery Days is part of the Bay Area Science Festival. The Festival hopes that by making this a fun event it will encourage kids – and that’s the main audience here – to think about pursuing a career in science.

Parents and teachers are an important part of it too. The event gives them both ideas and tools on how to make learning about and teaching science more enjoyable, to help them get young people thinking about science outside the classroom, and to get them to understand that everything they see and do – from throwing a baseball to building a house – involves science.

Engaging the public in science is more than just an academic exercise. In recent years we have seen some fairly sizable cuts in funding for health, medical and scientific research in the US. These cuts are already slowing down our ability to do the research that can lead to new treatments for deadly diseases. Public support for scientific research is essential if we are to stop the cuts and increase funding. Events like Discovery Days can not only educate the public on how fascinating science is, but also how essential public funding for it is.

Bay Area Science Fair logo

So come along tomorrow (November 1) to Discovery Days. The event runs from 11am to 4pm and it’s FREE. It’s at AT&T Park (did I mention that’s the home of the newly crowned champions of baseball, the San Francisco Giants).

Here’s how you can get there

Scientists Develop Stem Cell ‘Special Forces’ in order to Target, Destroy Brain Tumors

Curing someone of cancer is, in theory, a piece of cake: all you have to do is kill the cancer cells while leaving the healthy cells intact.

But in practice, this solution is far more difficult. In fact, it remains one of the great unsolved problems in modern oncology: how do you find, target and destroy each individual cancer cell in the body—while minimizing damage to the surrounding cells.

Encapsulated toxin-producing stem cells (in blue) help kill brain tumor cells in the tumor resection cavity (in green). [Credit: Khalid Shah, MS, PhD]

Encapsulated toxin-producing stem cells (in blue) help kill brain tumor cells in the tumor resection cavity (in green). [Credit: Khalid Shah, MS, PhD]

But luckily, Harvard Stem Cell Institute scientists at Massachusetts General Hospital may have finally struck gold: they have designed special, toxin-secreting stem cells that can target and destroy brain tumors. Their findings, which were performed in laboratory mice and which appear in the latest issue of the journal STEM CELLS, offer up an entirely unique method for eradicating deadly cancers.

Harvard Neuroscientist Khalid Shah, who led the study, explained in last Friday’s news release that the idea of engineering stem cells to kill cancer cells is not new—but there was a key difference in scientists’ ability to target individual cells vs. difficult-to-reach tumors, which is often the case with brain cancer:

“Cancer-killing toxins have been used with great success in a variety of blood cancers, but they don’t work as well in solid tumors because the cancers aren’t as accessible and the toxins have a short half-life.”

The solution, Shah and his team argued, was stem cells. Previously, Shah and his team discovered that stem cells could be used to circumvent these problems. The fact that stem cells continuously renew meant that they could also be used to continually deliver toxins to brain tumors.

“But first, we needed to genetically engineer stem cells that could resist being killed themselves by the toxins,” said Shah.

In this study, the research team introduced a small genetic change, or mutation, into the stem cells so that they become impervious to the toxin’s harmful effects. They then introduced a second mutation that allowed the stem cells to maintain and produce and secrete toxins throughout the cells’ lifetime—effectively giving it an unlimited supply of ammunition to use once it encountered the brain tumor.

They then employed a common technique whereby the toxins were tagged so that they only sought out and infected cancer cells—leaving healthy cells unscathed.

“We tested these stem cells in a clinically relevant mouse model of brain cancer,” Shah described. “After doing all of the molecular analysis and imaging to track the inhibition of protein synthesis within brain tumors, we do see the toxins kill the cancer cells and eventually prolonging the survival in animal models.”

While preliminary, these results are encouraging. As the team continues to refine their method of development and delivery, they are optimistic that they can bring their methods to clinical trial within the next five years.

Stem Cell Stories that Caught our Eye: A Zebrafish’s Stripes, Stem Cell Sound Waves and the Dangers of Stem Cell Tourism

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.

The zebrafish (Danio rerio) owes its name to a repeating pattern of blue stripes alternating with golden stripes. [Credit: MPI f. Developmental Biology/ P. Malhawar]

The zebrafish (Danio rerio) owes its name to a repeating pattern of blue stripes alternating with golden stripes. [Credit: MPI f. Developmental Biology/ P. Malhawar]

How the Zebrafish Got its Stripes. Scientists in Germany have identified the different pigment cells that emerge during embryonic development and that determine the signature-striped pattern on the skins of zebrafish—one of science’s most commonly studied model organisms. These results, published this week in the journal Science, will help researchers understand how patterns, from stripes to spots to everything in between, develop.

In the study, scientists at the Max Planck Institute for Developmental Biology mapped how three distinct pigment cells, called black cells, reflective silvery cells, and yellow cells emerge during development and arrange themselves into the characteristic stripes. While researchers knew these three cell types were involved in stripe formation, what they discovered here was that these cells form when the zebrafish is a mere embryo.

“We were surprised to observe such cell behaviors, as these were totally unexpected from what we knew about color pattern formation”, says Prateek Mahalwar, first author of the study, in a news release.

What most surprised the research team, according to the news release, was that the three cell types each travel across the embryo to form the skin from a different direction. According to Dr. Christiane Nüsslein-Volhard, the study’s senior author:

“These findings inform our way of thinking about color pattern formation in other fish, but also in animals which are not accessible to direct observation during development such as peacocks, tigers and zebras.”

Sound Waves Dispense Individual Stem Cells. It happens all the time in the lab: scientists need to isolate and study a single stem cell. The trick is, how best to do it. Many methods have been developed to achieve this goal, but now scientists at the Regenerative Medicine Institute (REMEDI) at NUI Galway and Irish start-up Poly-Pico Technologies Ltd. have pioneered the idea of using sound waves to isolate living stem cells, in this case from bone marrow, with what they call the Poly-Pico micro-drop dispensing device.

Poly-Pico Technologies Ltd., a start-up that was spun out from the University of Limerick in Ireland, has developed a device that uses sound energy to accurately dispense protein, antibodies and DNA at very low volumes. In this study, REMEDI scientists harnessed this same technology to dispense stem cells.

These results, while preliminary, could help improve our understanding of stem cell biology, as well as a number of additional applications. As Poly-Pico CEO Alan Crean commented in a news release:

“We are delighted to see this new technology opportunity emerge at the interface between biology and engineering. There are other exciting applications of Poly-Pico’s unique technology in, for example, drug screening and DNA amplification. Our objective here is to make our technology available to companies, and researchers, and add value to what they are doing. This is one example of such a success.”

The Dangers of Stem Cell Toursim. Finally, a story from ABC News Australia, in which they recount a woman’s terrifying encounter with an unproven stem cell technique.

In this story, Annie Levington, who has suffered from multiple scleoris (MS) since 2007, tells of her journey from Melbourne to Germany. She describes a frightening experience in which she paid $15,000 to have a stem cell transplant. But when she returned home to Australia, she saw no improvement in her MS—a neuroinflammatory disease that causes nerve cells to whither.

“They said I would feel the effects within the next three weeks to a year. And nothing – I had noticed nothing whatsoever. [My neurologist] sent me to a hematologist who checked my bloods and concluded there was no evidence whatsoever that I received a stem cell transplant.”

Sadly, Levington’s story is not unusual, though it is not as dreadful as other instances, in which patients have traveled thousands of miles to have treatments that not only don’t cure they condition—they actually cause deadly harm.

The reason that these unproven techniques are even being administered is based on a medical loophole that allows doctors to treat patients, both in Australia and overseas, with their own stem cells—even if that treatment is unsafe or unproven.

And while there have been some extreme cases of death or severe injury because of these treatments, experts warn that the most likely outcome of these untested treatments is similar to Levington’s—your health won’t improve, but your bank account will have dwindled.

Want to learn more about the dangers of stem cell tourism? Check out our Stem Cell Tourism Fact Sheet.

A Cool New Way of Raising Funds and Awareness

Raising money to help fight a disease is tough. Trying to raise awareness about the disease can be just as tough. Doing both together is positively masochistic; an experience that is often as rewarding as dumping a bucket of ice cold water over your head.

Have you taken the ALS Ice Bucket Challenge?

Have you taken the ALS Ice Bucket Challenge?

And that’s precisely what a growing number of people around the country are doing to raise awareness about—and money for research into—Amyotrophic Lateral Sclerosis (ALS) also known as Lou Gehrig’s disease. They are dumping buckets of ice-cold water on their head.

It’s called, not surprisingly, the Ice Bucket Challenge. The idea behind it is simple. You dare someone you know to dump a bucket of ice cold water over their head within the next 24 hours or make a donation to help fight ALS. Once the person you have challenged either completes the challenge or makes a donation they then challenge other people—usually three other people—to do the same. And of course there’s nothing stopping you both dumping the water on yourself and making a donation.

The idea started out with people who had ALS and their friends and family but it has quickly spread. Celebrities such as Facebook’s Mark Zuckerberg, singer/actor Justin Timberlake, TV newsman Matt Lauer and even New Jersey Governor Chris Christie have all taken the Challenge. In fact the campaign has gone viral with videos and pictures of people taking the Challenge popping up on social media – Facebook and Instagram in particular – at a bewildering rate.

It’s more than just an opportunity to laugh at a potential Presidential candidate taking a self-inflicted cold shower it’s also raising a ton of money. The ALS Association says it raised $4 million in donations between the end of July and August 12th. That’s more than three and a half times more than it raised during the same period last year. They have also added more than 70,000 new donors to their cause.

That money goes to research into finding new treatments for ALS because right now there is no effective therapy at all. It also goes to help people living with this nasty, debilitating and ultimately deadly disease.

In a blog on the ALS website Barbara Newhouse, the President and CEO of the ALS Association said:

“We have never seen anything like this in the history of the disease. We couldn’t be more thrilled with the level of compassion, generosity and sense of humor that people are exhibiting as they take part in this impactful viral initiative.”

What I love about this is not just that it is raising awareness and funds for a truly worthwhile cause but that it also shows how a little bit of creativity can create so much more interest in a disease, and the people suffering from it, than any amount of well-meaning, more traditional attempts at education.

At the Stem Cell Agency we have worked closely with our friends in the ALS Association for many years and they do terrific work (you can read about our funding on our ALS Fact Sheet). But it’s a relatively rare condition – only affecting some 30,000 people in the U.S. at any one time – so it always struggles to get people’s attention compared to bigger diseases such as Alzheimer’s or stroke. But with this campaign they have changed that. They have taken a simple idea, a simple challenge, and used it to open people’s eyes to what they can do to help fight back against a deadly disease.

I find that really refreshing. As refreshing as a bucket of water over my own head.

Kevin McCormack

Creaky Cell Machinery Affects the Aging Immune System, CIRM-Funded Study Finds

Why do our immune systems weaken over time? Why are people over the age of 60 more susceptible to life-threatening infections and many forms of cancer? There’s no one answer to these questions—but scientists at the University of California, San Francisco (UCSF), have uncovered an important mechanism behind this phenomenon.

Reporting in the latest issue of the journal Nature, UCSF’s Dr. Emmanuelle Passegué and her team describe how blood and immune cells must be continually replenished over the lifetime of an organism. As that organism ages the complex cellular machinery that churns out new cells begins to falter. And when that happens, the body can become more susceptible to deadly infections, such as pneumonia.

As Passegué so definitively put it in a UCSF news release:

“We have found the cellular mechanism responsible for the inability of blood-forming cells to maintain blood production over time in an old organism, and have identified molecular defects that could be restored for rejuvenation therapies.”

The research team, which examined this mechanism in old mice, focused their efforts on hematopoetic stem cells—a type of stem cell that is responsible for producing new blood and immune cells. These stem cells are present throughout an organism’s lifetime, regularly dividing to preserve their own numbers.

Molecular tags of DNA damage are highlighted in green in blood-forming stem cells. [Credit: UCSF]

Molecular tags of DNA damage are highlighted in green in blood-forming stem cells. [Credit: UCSF]

But in an aging organism, these cells’ ability to generate new copies is not as good as it used to be. When the research team dug deeper they found a key bit of cellular machinery, called the mini-chromosome maintenance helicase, breaks down. When that happens, the DNA inside the cell can’t replicate itself properly—and the newly generated cell is not running on all cylinders.

One of the first things that these old stem cells lose as a result is their ability to make B cells. B cells, a key component of the immune system, normally make antibodies that fight infection. As B cell numbers dwindle in an aging organism, so too does their ability to fight infection. As a result the organism’s risk for contracting dangerous illnesses skyrockets.

This research, which was funded in part by CIRM, not only informs what goes wrong in an aging organism at the molecular level, but also points to new targets that could keep these stem cells functioning at full capacity, helping promote so-called ‘healthy aging.’ As Passegué added:

“Everybody talks about healthier aging. The decline of stem-cell function is a big part of age-related problems. Achieving longer lives relies in part on achieving a better understanding of why stem cells are not able to maintain optimal functioning.”

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

This summer we’re sponsoring high school interns in stem cell labs throughout California as part of our annual Creativity Program. We asked those students to share their experiences through blog posts, photos and videos.

Today, we bring you an outstanding group video from CIRM Interns at City of Hope in Los Angeles, with their own special version of the popular song, “Let it Go” from the movie Frozen.

These students have without a doubt showcased their extensive scientific knowledge in one of the most creative ways we at CIRM have ever seen!

Without further ado, we present “Let it Grow.”

Stem Cell Stories that Caught our Eye: Multiple Sclerosis, Parkinson’s and Reducing the Risk of Causing Tumors

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.

Cell therapy for Parkinson’s advancing to the clinic. A decade-long moratorium on the transplant of fetal nerve tissue into Parkinson’s patient will end in two months when the first patients in a large global trial will receive the cells. BioScience Technology did a detailed overview on the causes for the moratorium and the optimism about the time being right to try again. The publication also talks about what most people in the field believe will be the long-term solution: moving from scarce fetal tissue to nerve cells grown from readily available embryonic stem cells. The author’s jumping off point was a pair of presentations at the International Society for Stem Cell Research in June, which we wrote about at the time. But the BioScience piece provides more background on the mixed results of earlier studies and references to recent journal publications showing long term—as much as 20 year—benefit for some of those patients.

It goes on to describe multiple reasons why, once the benefit is confirmed with fetal cells, moving to stem cells might be the better way to go. Not only are they more readily available, they can be purified in the lab as they are matured into the desired type of early-stage nerve cell. Researchers believe that some of the side effects seen in the early fetal trials stemmed from the transplants containing a second type of cell that caused jerking movements known as dyskinesias. One stem cell trial is expected to start in 2017, which we discussed in June.

Immunity persists through a special set of stem cells. Our immune system involves so many players and so much cell-to-cell interaction that there are significant gaps in our understanding of how it all works. One of those is how we can have long-term immunity to certain pathogens. The T-cells responsible for destroying invading bugs remember encountering specific ones, but they only live for a few years, generally estimated at five to 15. The blood-forming stem cells that are capable of generating all our immune cells would not have memory of specific invaders so could not be responsible for the long term immunity.

Now, an international team from Germany and from the Hutchison Center in Washington has isolated a subset of so-called “memory T-cells” that have stem cell properties. They can renew themselves and they can generate diverse offspring cells. Researchers have assumed cells like this must exist, but could not confirm it until they had some of the latest gee-wiz technologies that allow us to study single cells over time. ScienceDaily carried a story derived from a press release from the university in Munich and it discusses the long-term potential benefits from this finding, most notably for immune therapies in cancer. The team published their work in the journal Immunity.

Method may reduce the risk of stem cells causing tumors. When teams think about transplanting cells derived from pluripotent stem cells, either embryonic or iPS cells, they have to be concerned about causing tumors. While they will have tried to mature all the cells into a specific desired adult tissue, there may be a few pluripotent stem cells still in the mix that can cause tumors. A team at the Mayo Clinic seems to have developed a way to prevent any remaining stem cells in transplants derived from iPS cells from forming tumors. They treated the cells with a drug that blocks an enzyme needed for the stem cells to proliferate. Bio-Medicine ran a press release from the journal that published the finding, Stem Cells and Development. Unfortunately, that release lacks sufficient detail to know exactly what they did and its full impact. But it is nice to know that someone is developing some options of ways to begin to address this potential roadblock.

Multiple sclerosis just got easier to study. While we often talk about the power of iPS type stem cells to model disease, we probably devote too few electrons to the fact that the process is not easy and often takes a very long time. Taking a skin sample from a patient, reprogramming it to be an iPS cell, and then maturing those into the adult tissue that can mimic the disease in a dish takes months. It varies a bit depending on the type of adult tissue you want, but the nerve tissue that can mimic multiple sclerosis (MS) takes more than six months to create. So a team at the New York Stem Cell Foundation has been working on ways to speed up that process for MS. They now report that they have cut the time in half. This should make it much easier for more teams to jump into the effort of looking for cures for the disease. ScienceCodex ran the foundations press release.

Stem Cells become Tool to Screen for Drugs; Fight Dangerous Heart Infections.

A Stanford study adds a powerful example to our growing list of diseases that have yielded their secrets to iPS-type stem cells grown in a dish. These “disease-in-a-dish” models have become one of the most rapidly growing areas of stem cell science. But this time they did not start with skin from a patient with a genetic disease and see how that genetic defect manifests in cells in a dish. Instead they started with normal tissue and looked at how the resulting cells reacted to viral infection.

They were looking at a nasty heart infection called viral myocarditis, which can begin to cause damage to heart muscle within hours and often leads to death. Existing antiviral drugs have only a modest impact on reducing these infections. So even though there is an urgent need to find better drugs, animal models have not proven very useful and there is no ready supply of human heart tissue for lab study.

To create a ready supply of human heart tissue Joseph Wu’s CIRM-funded team at Stanford started with skin samples from three healthy donors, reprogrammed them into iPS cells and then matured those into heart muscle tissue. Then they took one of the main culprits of this infection, coxsackievirus, and labeled it with a fluorescent marker so they could track its activity in the heart cells.

They were able to verify that the virus infected the cells in a dish just as they do in normal heart tissue. And when they tried treating the cells with four existing antiviral drugs they saw the same modest decrease in the rate of infected cells seen in patients. For one of the drugs that had been shown to cause some heart toxicity, they also saw some damage to the cells in the dish.

They propose that their model can now be used to screen thousands of compounds for potentially more effective and safer drugs. They published their results in Circulation Research July 15.