Making a Think Tank think again; opening eyes to stem cell research


It’s not often you hear gasps of amazement from an audience, particularly not when that audience is a highly educated, very influential, not-easily-impressed group of people. But a panel presentation at the Milken Global Conference yesterday did just that, by describing the game-changing potential of stem cell therapies.

The Milken Global Conference is an extraordinary event in its own right. Over the course of three days of top-level presentations the conference draws together world leaders and prominent figures in the fields of finance, science and health – people like former British Prime Minister Tony Blair, Zappos CEO Tony Hsieh, NIH Director Dr. Francis Collins, and singer Will.i.am. The goal is to bring these minds together to solve urgent social and economic challenges and improve lives.

The audience for these presentations, as you might guess, has come to expect the very best. This is a tough crowd to impress. Fortunately the four panel members talking about stem cell research are not just skilled and experienced scientists, they are also articulate, engaging and witty. Now I might be a tad biased about this because all four just happen to be doing work that is funded by the stem cell agency.

Each explored a different aspect of stem cell research. Eugene Brandon from biotech company ViaCyte began with a basic description of what embryonic stem cells are and what they can do and, most importantly, how they are using that knowledge to develop a treatment for type 1 diabetes that we hope will enter a clinical trial later this year.

Paula Cannon from USC talked about combining stem cells with other technologies. In this way she believes scientists can genetically modify blood stem cells to develop a treatment, even a potential cure, for HIV/AIDS.

Jill Helms from Stanford explained how she is using stem cells to stimulate the body’s own healing mechanisms and how that can improve our ability to fight a wide range of age-related problems; from broken bones that don’t mend or wounds that don’t heal.

Alysson Muotri of UC San Diego rounded out the presentation talking about the use of iPS cells to create new ways of seeing how diseases impact particular cells in our body, and then using those cells to screen for potential new drugs to treat those diseases.

Even though the session was just one hour, it covered a lot of ground. Both the main room and the overflow room were packed. Clearly there is a lot of interest in the topic. And after the session many people came up to ask follow-up questions.

Those of us who are immersed in this world every day can sometimes forget just how extraordinary some of this research is, so it’s always a wonderful reminder to see the impact it has on people who are hearing about it for the first time. And it’s an incentive for us to make sure we tell our story to as many people as possible. After all, we have a great story to tell. kevin mccormack

Scientists Reprogram Mature Blood Cells to Generate Elusive Blood Stem Cells

Image: Derrick Rossi [credit: Boston Children’s Hospital]

It’s one of regenerative medicine’s most sought-after goals, but also one of the most difficult to reach: figuring out how to produce blood-forming hematopoietic stem cells, or HSCs. But now, researchers at the Harvard Stem Cell Institute at Boston Children’s Hospital have identified a stem cell-based technique that has the potential to do just that.

These types of cells, which form the basis of all our various blood cells, are in high demand for much-needed bone marrow transplants that treat various blood disorders such as leukemia. However, in nature HSCs are extremely rare. And previous stem cell-based therapies have been unable to generate HSCs that are suitable for transplantation. For example, check out this 2008 workshop whereby Cornelius Murre explains the difficult process of transforming stem cells into blood cells. Those difficulties persisted and still perplexed researchers attending an international workshop CIRM convened on the topic last summer.

Enter Boston Children’s Hospital’s Derrick Rossi. An expert in stem cell biology, Rossi was able to physically reprogram mature blood cells from mice into cells that looked and acted just like HSCs. They describe their results in the journal Cell. They called these new cells induced HSCs, or iHSCs. As Rossi explained in a recent news release:

“Blood cell production invariably goes in one direction: from stem cells, to progenitors, to mature…cells. We wanted to reverse the process and derive HSCs from differentiated blood cells using transcription factors that we found were specific to HSCs.”

These ‘transcription factors’ came in the form of eight genetic switches that were inserted into the mice’s mature blood cells in order to kick-start the cellular reprogramming process. The results were iHSCs in mice that were capable of recapitulating all blood cell types. As the study’s co-author Stuart Orkin added in the same news release:

“In the blood research field, no one has the conditions to expand HSCs in the tissue culture dish. Instead, by letting the reprogramming occur in [the cells of] mice, Rossi takes advantage of the signaling and environmental cues that HSCs would normally experience.”

While promising, there is still more work to be done, Rossi adds. For example, while the technique works in mice, there may be a different set of factors required to transform human blood cells into iHSCs. But Rossi and his research team have been bolstered by the results of this study and what it could mean for the future of bone marrow transplants—a future in which the patient’s own mature blood cells can be transformed into cells suitable for transplantation.

Anne Holden

Kids and their parents turn out on mass in nation’s capital to learn about science and engineering

Wow. What a weekend. We don’t have the official numbers yet, but it sure felt like the organizers met their projections of 200,000 plus attendees at the USA Science and Engineering Festival. Exhibitors offering the kids the chance to see or participate in hands-on science filled two entire floors of the Washington convention center. And the kids and parents jammed both floors—as you can see from the photo above—for the bulk of nine hours both days.

Exhibitors ran the gamut from government agencies and universities to science trade associations and industry. Caterpillar brought small bulldozers and forklifts that were predictably popular with the junior Y chromosome set. But we had a constant flow of kids of all ages, genders and ethnicities at our booth learning where stem cells come from and how to create scaffolds to hold stem cells to grow knee cartilage or ears. The latter had sufficient ick factor to be very popular with the pre-teens.

What was more exciting for my CIRM colleagues and I at the booth was the engagement of the parents. They like the chance to understand a bit more about “those stem cells we keep hearing about,” and to hear about some of the progress we are making toward therapies.

CIRM joined the International Society for Stem Cell Research and the Alliance for Regenerative Medicine in organizing and staffing the event. Together, these three organizations are probably the largest players in the field and while we often work together with one of the organizations or the other, this was the first time all three of us came together on a project. That, too, made the day feel special.

Then, this morning our communication and education committee for the Alliance met as part of the group’s annual D.C. board meeting. All agreed that the event was a great success and that we would come together to do more programs like this.

Don Gibbons

Genetic Analysis of 115 Year-Old Offers New Hints to the Limits of Human Longevity

New genetic analysis of a 115 year-old ‘supercentenerian’ reveals surprising clues as to what really helps people lead a long, healthy life free of disease—and what may be the underlying culprit that eventually helps contribute to their death.
Mutations, or ‘errors’ in a person’s genetic code have been linked to many devastating diseases, including blood cancers such as acute myeloid leukemia. But scientists had yet to examine the blood cells of healthy individuals to see whether they too, harbored similar mutations.
So, an international team of researchers collected a blood sample from a woman who, at the time of her death in 2005, was the oldest person in the world at 115 years old. And their results, published this week in Genome Research were shocking.
Using advanced whole-genome analysis, the team counted upwards of 400 mutations in the DNA extracted from the woman’s white blood cells—a number far higher than expected, thus revealing that the sheer amount of mutations accumulated is not the sole indicator of disease. But the more interesting finding came when the team examined another type of cell in the sample, the hematopoietic stem cell, or HSC.
HSCs are the ‘precursors’ to both white and red blood cells. They are stored in the bone marrow and continually replenish a person’s blood supply over time. It is this replenishing—the constant generation of new cells—that can cause genetic mutations in the cells’ DNA to develop over time. In this case, they found that even the blood cells of a healthy, supercentenerian were full of mutations. But the real bombshell was when the team examined the woman’s HSCs. As the study’s lead author Henne Holstage explained in a recent news release:

“To our great surprise we found that, at the time of her death, the…blood was derived from only two active hematopoietic stem cells—which were related to each other.”

Why were only these two cells helping to replenish the blood supply? Holstage and his team have a hypothesis, based on the lengths of the telomere. The telomere is a stretch of DNA at each end of each of our 23 pairs of chromosomes. Its job is to protect the chromosome—and the DNA that comprises it—from degrading over time. The telomeres of the supercentenerian’s blood cells were remarkably short, and were thus not as adept at protecting the cells’ DNA.

“Because these blood cells had extremely short telomeres, we speculated that most [of the other] hematopoietic stem cells may have died from ‘stem cell exhaustion,’ reaching the upper limit of stem cell division.”

In future studies, Holstage and his team will further delve into this concept of ‘stem cell exhaustion.’ Even so, these early findings point to new understanding of how stem cells are a vital component to maintaining health—even at a very advanced age.
They also highlight the growing relationship between the two fields of genetics and stem cell biology, a relationship that CIRM recently agreed to foster with our new Genomics Initiative.
Anne Holden

The art of science, the science of art

Most of us tend to think of art and science as being two very different subjects. They certainly were in my high school where I frequently got in trouble for doodling when I should have been paying attention to the chemistry teacher. But increasingly today we are seeing efforts to show that the two are not just related, but connected and complementary.

Kelly Milukas is an artist who is trying to bring the worlds of art and science together in a way that both engages and informs. Milukas uses the symbolism of keys as a way to illustrate how science attempts to unlock the mysteries of the human body. She also explores the world of regenerative medicine by showing the beauty of stem cells as seen through pictures taken with microscopes. They’re not only important from a scientific perspective; they are also stunning works of art.

Kelly’s work was originally commissioned by the Regenerative Medicine Foundation (RMF) for an exhibition in Palm Beach, Florida. RMF cites as part of its mission the need to explore “the body’s natural ability to heal itself.”

Now RMF and Kelly are bringing that message, and that art, to the San Francisco Bay Area. Kelly will be presenting her art and talking about the inspiration behind it in a special free public event as part of the RMF’s national conference on Monday, May 5th at 6.30pm at the Claremont Hotel in Berkeley.

The presentation is called “Keys to the Cure & the Art of Science: Unlocking the Body’s Ability to Heal Itself.” The art will be used as a springboard for a wider discussion about stem cells and regenerative medicine featuring one of the world’s best know stem cell scientists, Dr. Anthony Atala, Director of the Wake Forest Institute for Regenerative Medicine. Atala is best know for his research using stem cells, and a 3D printer, to create new tissues and organs. Alongside Atala will be two great friends of the stem cell agency, Patient Advocates Katie Jackson and Don Reed.

A news release put out by RMF has all the details of the event.

A mirror image event, called “Stem Cells Offer Hope”, is being held at U.C. Irvine on Thursday,  May 1. This features powerful images of stem cells that represent hope for people battling deadly diseases.

In a news release about the event Sidney Golub, Ph.D., Director of the Sue & Bill Gross Stem Cell Research Center says:

“As researchers, we are often awed by these microscopic stem cells and the enormity of their contributions to the growth and repair of the human body. We chose images from our research studies that capture the excitement of what these cells will accomplish. Once we unlock their potential, it will change the way medicine is practiced.” 

At the University of Southern California they are using art to break down barriers. They got two groups of students, one studying art and design and the other stem cell biology, to collaborate on a project to try and come up with a new way of communicating about stem cells.

The results ranged from a watercolor of zebrafish skull images,as seen under a microscope, to a giant environmental design project for the USC stem cell building.

The works are not just visually engaging, according to Andy McMahon, head of USC Stem Cell, they also serve a valuable purpose:

“Beyond the works of art that have been forged through this collaboration, scientists have improved their ability to communicate with non-scientists, and art students have learned the beauty of science through first-hand lab experience. This has expanded our perspectives and our worlds.”

And in the end isn’t that what both science and art try to do, to change the world we live in, and to change the way we see that world.

kevin mccormack

Stem Cell Scientist Paul Knoepfler Interviewed for Studio Sacramento

Above: Paul Knoepfler speaks on Studio Sacramento.

What secrets do stem cells hold? And how are scientists using them to better understand and treat deadly diseases such as ALS, Alzheimer’s and AIDS?

Last week UC Davis resident stem cell expert Paul Knoepfler sat down with Scott Syphax of Studio Sacramento to talk about the promise of stem cell biology and regenerative medicine.

In this comprehensive interview Knoepfler touches on a variety of topics—including the importance of CIRM as the research progresses from the lab bench into the clinic.

Watch the full video here, and be sure to check out more from Knoepfler, including this video on why embryonic stem cells have a tendency to form tumors.

Anne Holden

Tumor Cells Become Drug Resistant by Reverting to a Stem Cell-Like State, New Study Finds

It’s every cancer patient’s fear: that the drugs being used to shrink their deadly tumor stop working.

Faced with this stark reality, researchers have become trapped in a molecular ‘arms race,’ trying to develop more effective therapies to attack the cancer. A better solution would be to prevent the drug resistance at the outset, but thus far scientists have struggled to understand the underlying mechanism of resistance.

Now, scientists at the University of California, San Diego School of Medicine have discovered a molecule on the surface of tumors that appears to promote resistance—by converting the tumor cells back into a stem cell-like state. The results, published in Sunday’s issue of the journal Nature Cell Biology, point to a new way to cut off drug-resistant tumors at the source.

Drug-resistant cancer is a persistent problem that has plagued the oncology community and doctors are desperate for a new solution. As the study’s lead author and David Cheresh points out in a recent news release,

“There are a number of drugs that patients respond to during their initial cancer treatment, but relapse occurs when cancer cells become drug-resistant. We looked at the cells before and after they became resistant and asked, ‘what has changed in the cells?’”

In order to answer that question, the research team focused their efforts on two commonly used cancer drugs, erlotinib and lapatinib, monitoring the physical and chemical properties of individual tumor cells as they were treated with the drugs over time. And what they found taking place was a very peculiar transformation.

When the tumor cells began to exhibit drug resistance, the cells were simultaneously transforming into a stem cell-like state, which made them impervious to the drugs. In effect, they were able to hide from the drugs in plain sight. Importantly, these findings shed new light on cancer stem cells, the existence of which has long been a subject of debate among the medical community. This study could generate a chicken-and-egg debate about what comes first, cancer stem cells or the original tumor, or do stem cell-like cancer cells exist at two points in time.

Most troublingly, explained Cheresh, was that it appeared that the treatment itself was driving this transformation by activating a specific molecular pathway.

Luckily, the team also identified several existing drugs that attack this pathway and reverse the cellular transformation, thus ‘re-sensitizing’ the tumor. And within the next year, Hatim Husain at the Moores Cancer Center in La Jolla, CA will begin a clinical trial testing the effectiveness of this strategy in patients with drug-resistant lung cancer. As Husain explained in the same news release:

“Based on these research findings we now better understand how to exploit the ‘Achilles Heel’ of these drug-resistant tumors.”

Husain and his colleagues are optimistic that combination therapies that keep the disease under control, but also combat drug resistance, are our best bet for reducing mortality and improving quality of life.

Eventually, he hopes that treatments can evolve to such a level that they can prevent drug resistance before it even begins. This is welcome news for the millions of patients and their families who must constantly wage new battles each time their cancer becomes drug resistant.

To find out how CIRM-funded scientists are harnessing the power of stem cells to fight cancer, check out our disease programs in leukemia, brain cancer and melanoma.

Photo caption: In the above image, drug-resistant tumor cells are shown in brown [Credit: UC San Diego School of Medicine]

Anne Holden

Children and parents to get a hands-on experience in stem cell science at the U.S. Science and Engineering Festival this weekend

Young people making Play Doh stem cells at last fall’s Bay Area Science Festival

We spend a great deal of time and effort at CIRM creating ways for the general public to stay informed about stem cell science. In particular I have an extra mandate to make sure we don’t forget about the young ones. That is why I developed a stem cell high school curriculum and get out to college campuses a few times a year; it is just fun to talk to young people.

But science festivals ratchet that up about a dozen notches. For the past two years we have participated in the Bay Area Science Festival, which attracts more than 20,000 children and their parents to the San Francisco Giants baseball park. Most of the kids range from age 5 to age 15 and their excitement in getting the chance to participate in hands-on science is palpable. It is also important to note that while the kids are playing with the activity, the parents seem genuinely pleased to get a chance to talk about what we are accomplishing in stem cell science.

Now, CIRM has teamed up with the International Society for Stem Cell Research and the Alliance for Regenerative Medicine to offer two hands-on activities at the third annual USA Science and Engineering Festival
For younger kids we will be offering them the chance to make stem cells out of Play Doh. And for older ones, they can participate in a tissue engineering exercise in which they can inject alginate, a gel-like substance made from seaweed, into molds of either an ear or a meniscus, the cartilage in the knee that many weekend warriors would love to have refreshed. The alginate sets in two minutes, so the kids can walk away with a baggie holding their body part, which in the lab would become a scaffold for seeding stem cells to grow the real thing.

If you have friends or family in the D.C. area, tell them to come to booth #706 at the Washington Convention Center Saturday or Sunday. It being the nation’s capital, I will be sorely disappointed if I don’t see at least one congressman or woman being a good parent and taking their children to get excited by science. Although, since the festival expects to attract over 200,000 people, the legislators could get lost in the crowd.

Don Gibbons

Shape-Shifting Stem Cells Could Inform New Wave of Absorbent Technologies

A unique, shape-shifting property—previously only identified in man-made materials—has been discovered to also exist in stem cells.

In a study published on Sunday in the journal Nature Materials, scientists at the University of Cambridge, UK, describe a strange event that occurred when observing the physical changes that occur as stem cells grow and mature into the various cell types in the body.

Most materials in nature, when stretched or squeezed, will then revert back to their original shape. But a select few materials will do the opposite: once stretched or squeezed they maintain their new shape. These so-called “auxetic materials,” which can act as a kind of super-absorbent sponge, are of great interest to materials scientists and engineers looking to improve methods to create everything from soundproofing to bulletproof vests.

In this study, the research team—made up of biologists, engineers and physicists—were completely shocked when they saw stem cells exhibiting distinct auxetic properties as they began to transform into tissue-specific cells. As the study’s lead author Kevin Chalut noted in a recent news release:

“When the stem cell is in the process of transforming into a particular type of cell, its nucleus takes on an auxetic property, allowing it to ‘sponge up’ essential materials from its surroundings. This property has not, to my knowledge, been seen before at the cellular level—and is highly unusual in the natural world.”

Chalut and his colleagues were able to spot this unique property by treating the fluid that surrounds the cell’s nucleus, called the cytoplasm, with a particular type of dye. As the cell transformed and matured into a tissue-specific cell, the nucleus absorbed the colored dye. This was an indication that the nucleus itself was expanding—perhaps in order to absorb key molecules residing in the cytoplasm that are required for a transformation.

This research stands to not only improve our understanding of stem cells’ underlying molecular biology, but also to inform the related fields of engineering and materials science. It is a strong reminder of the importance of basic research; that even as the field of regenerative medicine moves forward into the clinic, it is still vital for organizations such as CIRM to support and foster this type of research.

As CIRM-grantee Irv Weissman stated in a recent video on the importance of basic research:

“This happens over and over again in basic research. If you keep your mind open you will begin to see things.”

A biophysicist by training, Chalut agrees, stating that that his team’s discovery is just another indication of how much we still have to learn about nature:

“Despite great technological effort, auxetic materials are still rare and there is much to discover about them…. [But] studying how auxecity evolved in nature will guide research into new ways to produce auxetic materials, which might have many diverse applications in our everyday life.”

Anne Holden

Stanford Researchers Develop New Technique that can Map a Cell’s Genetic ‘Blueprint’

There are many different types of cells in the human body, but they all have something in common: housed within each is the complete set of genetic instructions, our genome, that give us life. It turns out that what makes cells different—what guides a blood cell to become a blood cell—depends on which parts of the genome are switched on, and which remain silent.

That much has become clear in recent years. But as far as the underlying molecular processes that guide these genetic ‘switches’? Scientists are still trying to figure out how it all works.

Luckily, a team of engineers at Stanford University made a significant break in the case: a way to map the growth of a single cell at the molecular level, gene by gene and day by day. The result: a procedure that effectively ‘reverse engineers’ a specific type of mature tissue from a single cell—knowledge that stands to improve scientists’ understanding of how cells transform from an all-purpose, stem cell-like state, into the various cell-types in the body.

The research team, led by Stephen Quake from the Stanford School of Engineering, focused on the types of lung cells that make up the alveoli, the small structures that serve as ‘docking stations’ for blood vessels to receive oxygen and expel carbon dioxide. In order to achieve their results, which were published in the April 13 issue of the journal Nature, the team required a few ingenious pieces of technology.

First, a specialized device, akin to a molecular ‘eye-dropper,’ that allows for collecting a single cell inside a chamber to study. And second, a way to detect the genes that were being switched on in that cell as it matured over time.

That specific set of tools, however, did not exist. So the research team built them. And in so doing, they were able to shed light on what had until now been a very nebulous process.

Using their newly developed tools, Quake and his team discovered that the two main types of alveolar cells, called (fittingly) alveolar type-1 and alveolar type -2, both derive from the same early-stage lung cell. This is despite significant physical differences and functions between the two types. The team’s technique also allowed them to capture cells at critical moments in time, for example as they transitioned from an early, stem cell-like state into a more mature alveolar-like cell.

Though pioneered in lung cells, this technology could be applied to a wide variety of cell types—and therein lies the rub. As Tushar Desai, the study’s co-author and an assistant professor at the Stanford University School of Medicine explained in a news release:

“This technique represents a quantum leap forward in our ability to apprehend the full diversity of cell types, including the rare ones that could have special functions. Because of a comprehensive molecular characterization of each [cell] type is achieved, a snapshot of the communication between individual cells will also emerge—and may suggest attractive therapeutic targets in disease.”

Indeed, this study highlights the important relationship between the fields of genomics and the stem cell research; a relationship that CIRM believes must be fostered, as evidenced by the creation of the new Center for Excellence in Stem Cell Genomics earlier this year. As CIRM President Alan Trounson stated in the January news release announcing the new Genetics Center:

“That deeper knowledge, that you can only get through a genomic analysis of the cells, will help us develop better ways of using these cells to come up with new treatments for deadly diseases.”

Anne Holden