Stem cell stories that caught our eye: brain repair, bone repair and boosting old stem 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.

Potential drugs to make brain stem cells do a better job.
Patients with strokes and neurodegenerative diseases usually have a double whammy of faulty self-repair mechanisms. The brain is one of those organs that has few adult stem cells and most patients are decidedly senior citizens with older stem cells that are less robust.

Most teams looking to get around that problem implant stem cells from young donors, but that can be invasive and the cells often don’t survive long in a non-native environment. So, several groups are looking for ways to get those few stem cells in our adult brain to do a better job. One team, at the Australian company Novogen, announced this week that they had discovered a class of compounds that seems to promote the growth and activation of adult brain stem cells.

Yahoo Finance picked up the company’s press release, which is a little excessively promotional, but does get the basic facts straight. If these compounds end up working in people, they could make a big difference in healing neural conditions.

Another option for boosting older stem cells. A team at Moscow State University has published a review of the research into why stem cells in older people are not as good at repairing damage, and some early attempts to boost the performance of those cells. The short write up of the paper in Genetic Engineering & Biotechnology News gives very little detail, but it does have a link to the full article in BioResearch Open Access, which is relatively understandable.
old mouse
They give some focus to the use of a patient’s mesenchymal stem cells from their bone marrow or fat to treat heart problems. They site a few studies that suggest if you stress the cells in the lab after you harvest them from the patient and before you inject the back to where they are needed, they seem to do a better job. In particular, they cited growing the cells in an extremely low-oxygen environment.

A new type of bone stem cell discovered.
The dogma has been that mesenchymal stem cells (MSCs) found in the bone give rise to any new bone or cartilage we may need as adults. But those cells also have roles making a few other types of cells. Now, researchers on both coasts, at Stanford and Columbia, have discovered a more specific stem cell that just gives rise to bone and cartilage.

Both research papers appeared in today’s online edition of the journal Cell and Genetic Engineering & Biotechnology News wrote up the Columbia study. It points out that while it remains true that MSCs can generate bone, the newly discovered cells may be more efficient doing it and may be better targets for therapies that try to speed bone healing. The university’s press release was picked up by ScienceDaily and provides a bit more detail.

The Stanford team, after isolating the bone-specific stem cells, took the work another step. That work could be key to helping older patients who often have slow healing fractures because they have fewer active stem cells of any type. The CIRM-funded researchers discovered a set of genetic factors that can be used to reprogram fat cells to become the specialized bone stem cell. In a press release picked up by HealthCanal one of the senior authors on the paper, Michael Longaker, described how the finding might allow patients to avoid the painful procedure of harvesting bone for bone grafts.

“Using this research you might be able to put some of your own fat into a biomimetic scaffold, let it grow into the bone you want in a muscle or fat pocket, and then move that new bone to where it’s needed.”


The cancer stem cell debate explained.
Jocelyn Kaiser wrote the best, most balanced, piece I have read on the whole debate over whether cancer stem cells exist, and more important, will targeting them really make a difference in the number of patients we cure of cancer? Even though it appears in the journal Science it is written as a feature and is pretty approachable to a lay audience.

A book for stem cell wonks.
David Warburton, a CIRM-grantee at Children’s Hospital Los Angeles, has published a book of essays that cover a broad swath of the field of regenerative medicine. The essays range from the minutia of what it takes to set up a stem cell lab to the pipeline of potential therapies. I have to admit I have a personal prejudice to like the book given his quote in the press release on EurekAlert:

“Those of us working in this field in California are positively impacted by the critical funding provided by the citizens of the state through the California Institute for Regenerative Medicine. I believe this book shows that the hope behind CIRM – the hope that stem cells can really revolutionize medicine and human health – is fully justified.”

In living color: new imaging technique tracks traveling stem cells

Before blood stem cells can mature, before they can grow and multiply into the red blood cells that feed our organs, or the white blood cells that protect us from pathogens, they must go on a journey.

A blood stem cell en route to taking root in a zebrafish. [Credit: Boston Children's Hospital]

A blood stem cell en route to taking root in a zebrafish. [Credit:
Boston Children’s Hospital]

This journey, which takes place in the developing embryo, moves blood stem cells from their place of origin to where they will take root to grow and mature. That this journey happened was well known to scientists, but precisely how it happened remained shrouded in darkness.

But now, for the first time, scientists at Boston Children’s Hospital have literally shone a light on the entire process. In so doing, they have opened the door to improving surgical procedures that also rely on the movement of blood cells—such as bone marrow transplants, which are in essence stem cell transplants.

Reporting in today’s issue of the journal Cell, Boston Children’s senior investigator Leonard Zon and his team developed a way to visually track the trip that blood stem cells take in the developing embryo. As described in today’s news release, the same process that guides blood stem cells to the right place also occurs during a bone marrow transplant. The similarities between the two, therefore, could lead to more successful bone marrow transplants. According to the study’s co-first author Owen Tamplin:

“Stem cell and bone marrow transplants are still very much a black box—cells are introduced into a patient and later on we can measure recovery of the blood system, but what happens in between can’t be seen. Now we have a system where we can actually watch that middle step.”

And in the following video, Zon describes exactly how they did it:

As outlined in the above video, Zon and his team developed a transparent version of the zebrafish, a tiny model organism that is often used by scientists to study embryonic development. They then labeled blood stem cells in this transparent fish with a special fluorescent dye, so that the cells glowed green. And finally, with the help of both confocal and electron microscopy, they sat back and watched the blood stem cell take root in what’s called its niche—in beautiful Technicolor.

“Nobody’s ever visualized live how a stem cell interacts with its niche,” explained Zon. “This is the first time we get a very high-resolution view of the process.”

Further experiments found that the process in zebrafish closely resembled the process in mice—an indication that the same basic system could exist for humans.

With that possibility in mind, Zon and his team already have a lead on a way to improve the success of human bone marrow transplants. In chemical screening experiments, the team identified a chemical compound called lycorine that boosts the interaction between the zebrafish blood stem cell and its niche—thus promoting the number of blood stem cells as the embryo matures.

Does the lycorine compound (or an equivalent) exist to boost blood stem cells in mice? Or even in humans? That remains to be seen. But with the help of the imaging technology used by Zon and the Boston Children’s team—they have a good chance of being able to see it.

Tick-Tock: How our daily body clock protects our stem cells

In our world of tweets, tablets, smartphones and social media, it’s hard to disengage from the always-on pace of modern life. This is in stark contrast to a camping trip. After a few days in the wilderness, you adjust to a more natural sync – waking at sunrise and heading to bed at sundown. Many biological processes fluctuate along with this day/night cycle called the circadian rhythm. This 24-hour body clock is known to regulate our sleep patterns, feeding behavior, body temperature and many other functions.

Features of the human circadian (24hr) rhythm. (credit: The Gladstone Institutes)

Features of the human circadian rhythm, a 24 hr day/night body clock. (credit: The Gladstone Institutes)

Now, in a fascinating study reported last week in Cell Reports, University of California, Irvine researchers show evidence that the circadian rhythm also protects skin stem cells from damage associated with accelerated aging and cancer.

First a little background: the outer skin layer, or epidermis, contains a long-lasting population of stem cells that multiply and grow into new skin cells to keep the skin healthy and heal it from injury. In order to multiply, a cell must copy its DNA and then divide. This process requires energy that ultimately comes from the metabolic breakdown of food that we eat. Herein lies a dangerous mix: the metabolism of food that supplies energy to these cells also generates a byproduct, a very reactive oxygen molecule that damages DNA and other parts of the cell. Dividing cells are especially vulnerable to the reactive oxygen. This damage can lead to an accumulation of DNA mutations that are thought to be the underlying cause of aging and cancer.

By taking advantage of a non-invasive technique that uses sophisticated microscopes, the UC-Irvine research team examined the metabolic activity of single stem cells within the skin of live mice. They found that the metabolic step that creates these toxic oxygen molecules peaks during the daytime while previous studies have shown that the highest number of dividing cells occurs in the night. So the circadian rhythm ensures that stem cell division steers clear of the DNA damaging effects of metabolism and the two activities do not peak at the same time during the course of each day.

Dr. Bogi Anderson, UC Irvine professor of biological chemistry and medicine. (credit: Paul R. Kennedy)

Dr. Bogi Anderson, UC Irvine professor of biological chemistry and medicine. (credit: Paul R. Kennedy)

The research team, led by Bogi Andersen, professor of biological chemistry and medicine, and Enrico Gratton, professor of biomedical engineering, further shows that mice lacking Bmal1, a gene essential for the circadian rhythm, no longer have this daily metabolic fluctuation. Presumably more DNA damage would occur in these mice and in fact, other researchers have shown that mutations in Bmal1 are associated with premature aging and increased DNA damage.

Taken all together maybe there’s some truth to the idea that our frenetic modern life is dangerous for our health. As Dr. Andersen states in a press release:

“Our studies were conducted in mice, but the greater implication of the work relates to the fact that circadian disruption is very common in modern society, and one consequence of such disruption could be abnormal function of stem cells and accelerated aging. It is possible that future studies could advance therapeutic insights from this research.”

Strong ARMing regenerative medicine; bold thoughts on a bright future

It’s a time-honored tradition for the President of the United States to begin his State of the Union speech by saying “The state of our union is strong.” Well, Ed Lanphier, the incoming Chairman of the Alliance for Regenerative Medicine (ARM) – the industry trade group – took a leaf out of that book in kicking off the annual “State of the Industry Briefing” in San Francisco yesterday. He said the state of the industry is not just strong, but getting stronger all the time.

ARM_State_of_the_Industry_Briefing_2015_And he had the facts to back him up. In monetary terms alone he said the regenerative medicine field raised $6.3 billion in 2014, compared to $2.3 billion in 2013.

He pointed to the growing number of partnerships and alliances between big pharmaceutical businesses and smaller biotech and cell therapy companies as a sign that deep pocket investors recognize the potential in the field, saying “Big Pharma sees the value of these outcomes and the maturation of these pipelines.”

Lanphier also highlighted the more than 375 clinical trials that were underway last year, and the fact that more than 60 regenerative medicine products have been approved.

But he also pointed out that the field as a whole faces some big challenges in the coming years. One of the most pressing could be pricing. He cited criticisms that exploded over medicines like Gilead’s hepatitis C treatment Sovaldi because of its $1,000-a-day price tag. Lanphier warned that regenerative medicine could face similar criticisms when some of its therapies are finally approved, because they are likely to be very expensive (at least to start with). He said we need to start thinking now how to talk to patients and the public in general about this, so they understand why these treatments are so expensive, but may be cheaper in the long run if they cure rather than just treat disease.

As if to reinforce that message the first panel discussion in the briefing focused on the gene therapy and genome-editing field. Panel members talked about the high expectations for this field in the 1990’s but that it took decades of work before we finally started to see those early hopes turn into reality.

Jeffrey Walsh, the COO of bluebird bio talked about: “The excitement about gene therapy in the early days… and then having to survive the 15-20 years after that in the very challenging days for gene therapy.”

Katrine Bosley, the CEO of Editas Medicine, says those challenges have not gone away and that the field will have to address some big issues in the future. Among those are working with regulatory agencies such as the Food and Drug Administration (FDA) to win approval for completely new ways of treating disease. Another is anticipating the kinds of ethical issues they will have to address in using these techniques to alter genes.

Questions about the regulatory process also popped up in the second panel, which focused more on advanced therapy and drug development. Paul Laikind of ViaCyte (whose clinical trial in type 1 diabetes we are funding) highlighted those challenges saying: “Making the cells the way you want is not rocket science; but doing it in a way that meets regulatory requirements is rocket science.”

Paul Wotton, the President and CEO of Ocata Therapeutics (formerly called ACT) echoed those sentiments:

“We are pioneering things here and it’s the pioneers who often end up with arrows in their back, so you really have to spend a lot of time working with the FDA and other regulatory bodies to make sure you are having all the right conversations ahead of time.”

But while everyone freely acknowledged there are challenging times ahead, the mood was still very positive, perhaps best summed up by C. Randal Mills, the President of CEO of CIRM and moderator of the panel, when he said:

“I find it remarkable where we are in this space today – with this number of cutting edge companies in clinical trials. Stem cell therapy is becoming a reality, it’s no longer a place where only a foolish few dare to go in; it’s a reality. There is a change in the practice of medicine that is coming and we are all fortunate to be a part of it.”

2015 Golden Globes shines light on Alzheimer’s and ALS with acting awards

In between the one-liners, surprise presenters and bottomless champagne, something remarkable happened at last night’s 72nd Golden Globe Awards.

26 awards were given last night to the best in film and television. But two in particular were especially meaningful.

Julianne Moore plays a professor grappling with Alzheimer's in Still Alice [Credit: Sony Pictures Classics]

Julianne Moore plays a professor grappling with Alzheimer’s in Still Alice [Credit: Sony Pictures Classics]

I am referring, of course, to Julianne Moore and Eddie Redmayne, who each took home awards in the lead acting categories for their portrayals of two individuals suffering from neurodegenerative diseases. Their wins not only solidified them as front-runners for the Academy Awards ceremony next month, but also gave millions of viewers a deeply intimate look at two unforgiving illnesses.

Eddie Redmayne as Stephen Hawking in The Theory of Everything [Credit: Focus Features]

Eddie Redmayne as Stephen Hawking in The Theory of Everything [Credit: Focus Features]

Renowned actress Julianne Moore was the first of the two to receive her award, winning for her role as Alice Howland, a Columbia linguistics professor diagnosed with Early-Onset Alzheimer’s disease, in the film Still Alice.

And later in the program the Globes honored Eddie Redmayne for his brilliant portrayal of Professor Stephen Hawking—a long-time sufferer of the motor neuron disease ALS—in the biopic The Theory of Everything.

These two films were particularly poignant for those in the Alzheimer’s and ALS communities—as they reveal in stark, sometimes disturbing detail, how these diseases wreak havoc on the brain and nervous system. In preparation for their roles, each spent several months speaking with patients and clinicians who see and live with the diseases every day.

For example, Moore spoke with women who—like her character Alice—were living with Early-Onset Alzheimer’s, giving her first-hand knowledge of not only how the disease affects them, but also how their families are affected.

Meanwhile, Redmayne spent significant time with Hawking himself, learning about his unique experience as a long-time ALS patient. In interviews Redmayne has said that Hawking was often present during filming. The time the two individuals spent with each other clearly paid off, and had a remarkable impact on the actor.

“It is a great privilege for me to be in this room,” Redmayne said during his Golden Globe acceptance speech. “Getting to spend time with Stephen Hawking … was one of the great, great honors of my life.”

The fact that the two lead acting awards put spotlight on these diseases was not lost on the patient advocacy communities. For example, Maria Shriver tweeted shortly after the awards ceremony:

Shriver Tweet

Shriver’s statement underscores the stark reality of awareness, or lack thereof, for neurodegenerative diseases. Here at CIRM, we are laser focused on supporting ground-breaking work in regenerative medicine that can slow, halt or even reverse these conditions. We are hopeful that these two actors’ stellar performances can help put a human face on conditions that are all too-often reduced to numbers.

This hope has thus far translated to these films’ audiences. For example, said one review of Still Alice from the New York Post:

Still Alice … presents a disease that can devastate any family, anywhere, with unsparing truth and great compassion.”

Read more about how regenerative medicine can change the face of Alzheimer’s and ALS on our Stories of Hope.

Stem cell stories that caught our eye: EU approves a cell therapy, second ALS treatment shows promise and new gut cells work

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.

Europe approves first 2nd generation stem cell therapy.
While blood stem cells in bone marrow have been used to treat patients with certain blood cancers for more than 40 years, it has been a long wait for other uses of stem cells to gain official nods from regulatory bodies. The first came in 2012 when Canada approved Prochymal a stem cell therapy for kids who have a severe immune reaction after bone marrow transplant for cancer. That therapy helps the patients regulate their immune response and can be life saving.

Now the European Medicines Agency has approved a therapy for repairing eyes with damaged corneas—the first of a new generation of stem cell therapies that replace or repair specific tissues. The therapy uses a type of stem cell found in the eye called a limbal stem cell. An Italian team pioneered the procedure that has successfully restored vision to scores of patients whose eyes were damaged by chemicals or burns. An official with the EMA noted the significance of this approval in an agency press release.

“This recommendation represents a major step forward in delivering new and innovative medicines to patients.”

The BBC broke the news with a brief story, and MSN followed up with a bit more detail. (And no, this did not happen “this week” but it did happen after we went dark for the holidays.) CIRM also funds work with limbal stem cells.

Second type of stem cells shows benefit for ALS patients. Over the past couple years we have been writing about positive early trial results from Neuralstem for its therapy using a nerve stem cell for treating patients with ALS, also called Lou Gehrig’s disease. This week the company Brainstorm reported data showing improvement in most of the patients treated with a type of stem cell found in bone marrow and fat, mesenchymal stem cells.

The Neuralstem trials used donor stem cells and the Brainstorm trial uses a patient’s own cells, hence the drug name NeuOwn. But they have be revved up in the lab so that they secrete large quantities of what are called neurotrophic factors, chemicals that seem to protect nerves from damage by the disease and potentially foster healing of already damaged nerves.

Eleven of 12 patients experienced a decrease in the rate of progression of this normally very aggressive disease. The Israeli company completed its early trials in Israel but began a second stage trial at Massachusetts General Hospital in April. Reuters ran a story about the announcement.

New intestine engineered from stem cells. CIRM-grantee Tracy Grikscheit has previously reported growing tissues that look like intestinal cells and that have all the right cellular dog tags of our guts. Today the university announced she has shown she can grow tissues that actually function like our guts. They can absorb life-sustaining nutrients.

Because her work focuses on the devastating condition that results when a baby is born with insufficient intestine, it was not surprising this morning to find a good story about her work on the web site MotherBoard. The site quotes her on the latest advance:

“What’s important about this study is it’s not just taking pictures of the cells and saying ok, they’re in the proper location. We’re actually also looking at the function, so we’re showing that not only are the cells present that would for example absorb the sugar in your breakfast, but they actually are doing that job of absorbing sugar.”

Grikscheit works at Children’s Hospital Los Angeles and you can read about her CIRM-funded work to build new intestine here.


Luck’s role in stem cell mutations key to cancer.
Most of the popular talk about risk and cancer centers on inheriting bad genes and being exposed to nasty chemicals in our daily lives. But a new study says the biggest risk is more akin to a roulette wheel.

A study published in Science by a team at Johns Hopkins looked at 31 types of tissue in our bodies and found that random mutations that occur while our tissue-specific stem cells divide correlates better with cancer risk than what we inherit or environmental risks combined. The Scientist produced one of the more thoughtful pieces of the many on the research that appeared in the media this week.

A personal story about getting into stem cell research. I enjoy hearing about how people get into this fascinating field and the media team at the University of Southern California has provided a good example. They profile recent recruit, Michael Bonaguidi who explains how he made the switch from physical to biological science:

“Growing up on Legos and Lincoln Logs, I was very fascinated with building things. As I took more biology courses and was exposed to other facets of science — from chemistry to physics — I became more interested not in the outside but within. And that’s what got me into bioengineering versus structural engineering.”

Described as shaping brains instead of cities he is looking for the types of cells that can rebuild the brain after injury or stroke. HealthCanal picked up the university’s feature.

Multitasking molecule repairs damaged nerve cells, scientists discover in ‘stunning’ research breakthrough

Every molecule in the body has a job to do—everything from maintaining healthy cell functions to removing dead or decaying cells requires a coordinated series of molecular switches to complete. There’s a lot we know about what these molecules do, but even more that we are still discovering.

The PSR-1 molecule, which normally clears out dead or dying nerve cells, has also been observed trying to repair them.

The PSR-1 molecule, which normally clears out dead or dying nerve cells, has also been observed trying to repair them.

And as reported in a pair of studies published this week in Nature and Nature Communications, a molecule that has long been known to clear out dying or damaged nerve cells also—amazingly—tries to heal them.

The molecule at the heart of these studies is called phophatidylserine receptor, or PSR-1 for short. PSR-1’s main job had been to target and remove cells that were dead or dying—a sort of cellular ‘cleanup crew.’

Some cells die because they’ve reached the end of their life cycle and are scheduled for destruction, a programmed cell death known as apoptosis. Other cells die because they have been damaged by disease or injury. In this study, scientists at the University of Colorado, Boulder and the University of Queensland (UQ) in Brisbane, Australia, discovered that not only does PSR-1 clear out dead cells, it tries to save the ones that haven’t quite kicked the bucket.

Specifically, the team observed PSR-1 literally reconnecting nerve fibers, known as axons, which had broken due to injury.

“I would call this an unexpected and somewhat stunning finding,” said one of the study’s lead authors Ding Xue in a news release. “This is the first time a molecule involved in apoptosis has been found to have the ability to repair severed axons, and we believe it has great therapeutic potential.”

Professor Ding Xue of the University of Colorado Boulder. [Credit: Casey A. Cass, University of Colorado]

Professor Ding Xue of the University of Colorado Boulder. [Credit: Casey A. Cass, University of Colorado]

Injuries to nerve cells that reside in the brain or spinal cord are particularly distressing because once damaged, the cells can’t be repaired. As a result, many research groups have looked to innovative ways of coaxing the cells to repair themselves. Xue and Hilliard see the potential of PSR-1 to be involved in such a strategy.

“This will open new avenues to try and exploit this knowledge in other systems closer to human physiology and hopefully move toward solving injuries,” said Hilliard.

The discovery of PSR-1’s role in axon repair is based off a key difference between cells undergoing programmed cell death and those that are dying due to injury.

During apoptosis, cells release a beacon to alert PSR-1 that they’re ready for removal. But when a nerve cell is injured, it sends out a distress signal. Explained Xue:

“The moment there is a cut to the nerve cell we see…a signal to PSR-1 molecules in the other part of the nerve that essentially says ‘I am in danger, come and save me.’”

While these experiments were performed in the model organism C. elegans (a small worm often used in this sort of research), the researchers are optimistic that a similar process is taking place in human nerve cells.

“Whether human PSR has the capacity to repair injured axons is still unknown. But I think our new research findings will spur a number of research groups to chase this question.”

Scientists identify gene that causes good protein to turn bad

shutterstock_200363513

There exists a protein that, most of the time, helps keep the growth of cancer cells in check. But every so often it does the opposite—with potentially deadly consequences.

But now, researchers have discovered precisely why this protein, known as TGF-beta, can perform such an abrupt about-face. The results, published today in the journal Science Signaling, shed light on potential therapies that can succeed where others have failed—and attack the most aggressive forms of cancer.

TGF-beta is a type of tumor suppressor, a protein that normally keeps cells from growing, dividing and multiplying too quickly, which is how most tumors originate. But scientists have long observed that in many forms of cancer, TGF-beta has switched sides: it becomes a tumor promoter fostering the out-of-control growth of cells.

In this study, scientists at the University of Michigan Comprehensive Cancer Center have figured out that a gene called Bub1 seems to be pulling the strings—essentially flipping the switch on TGF-beta. The finding that Bub1 played such an important role in regulating TGF-beta caught the team completely off guard. According to the paper’s senior author Alnawaz Rehemtulla:

“Bub1 is well-known for its role in cell division. But this is the first study that links it to TGF-beta. We think this may explain the paradox of TGF-beta as a tumor promoter and a tumor suppressor.”

The team reached this conclusion by screening gene candidates against lung cancer and breast cancer cells. After screening over 700 genes, they narrowed down the potential gene to Bub1.

Further experiments revealed that Bub1 physically binds to TGF-beta, turning it to a tumor promoter in the process. And when the team prevented Bub1 from binding to TFG-beta, essentially blocking it, TGF-beta never turned sides.

These initial results have left the research team optimistic, in large part because Bub1 is known to be active, or ‘expressed,’ in so many forms of cancer. So, if they can find a way to block Bub1 in one type of cancer, they may be able to do so with other types.

Even at this early stage, the team has developed a compound that could block Bub1. Initial lab tests show that this so-called Bub1 ‘inhibitor’ could shut off the gene without affecting surrounding regions. Said Rehemtulla:

“When you look at gene expression in cancer, Bub1 is in the top five…. But we never knew why. Now that we have that link, we’re a step closer to shutting down this cycle.”

CIRM-funded scientists track the steps that take an adult cell back in time

The ability to transform an adult cell back into a stem cell has been heralded as one of the greatest achievements of the 21st century. Scientists have lauded this discovery, made by Nobel Prize-winning scientist Shinya Yamanaka, as a game changer for the future of medicine.

Despite this extraordinary advance, the method remains inefficient. And even the top experts still don’t quite understand how it works.

But now, a team of stem cell scientists from the University of California, Los Angeles (UCLA) has mapped the precise series of steps that an adult skin cell must go through to become a stem cell. The results, published online in the journal Cell, represent a much-needed step towards bringing cellular reprogramming forward.

A colony of iPSC's obtained by reprogramming a specialized cell for two weeks. The starting specialized cells can only make more of themselves, while the reprogrammed cells obtained from them can give rise to all cells of the body.

A colony of iPSC’s obtained by reprogramming a specialized cell for two weeks. The starting specialized cells can only make more of themselves, while the reprogrammed cells obtained from them can give rise to all cells of the body.

In this study, co-first authors Vincent Pasque and Jason Tchieu initiated the reprogramming process, whereby adult cells are reprogrammed back into embryonic-like stem cells. Yamanaka called these cells induced pluripotent stem cells, or iPSCs.

In order to map the steps being taken to reprogram these cells, the team devised a detailed time-course analysis whereby they would observe and analyze the cells each day as they transformed over a period of two weeks.

Importantly, the team found that no matter what type of adult cells were involved, the specific steps it took during reprogramming were the same. This revelation, that all adult cell types follow the same road map, is one of the most exciting discoveries. Said Pasque in a news release:

“The exact stage of reprogramming of any cell can now be determined. This study signals a big change in our thinking, because it provides simple and efficient tools for scientists to study stem cell creation in a stage-by-stage manner.”

The research team, led by CIRM grantee Katherin Plath, also uncovered some interesting information about the sequence of steps taken by these reprogrammed cells.

When an adult cell is reprogrammed back into an iPSC, it is not simply that all the steps that normally take an embryonic stem cell into an adult cell are reversed. Some may be reversed in the correct order, but others are not. And some steps are put off until the very end—indicating strong resistance against reprogramming.

“This reflects how cells do not like to change from one specialized cell type into another and resist a change in cellular identity,” said Pasque.

With future work, the team hopes to continue to investigate the reprogramming process. They are also hopeful that this newfound insight will bring robust iPSC-based therapies to the clinic.

CIRM 2.0: A New Year, a new start, a new way to advance research

It’s tradition to begin the New Year by making a resolution. Wikipedia has a wonderful description of what this involves saying it is where “a person makes a promise to do an act of self-improvement or something slightly nice, such as opening doors for people beginning from New Year’s Day.”

CIRM2.0_Logo

Well, by that criteria, CIRM 2.0 is a perfect way for us to start 2015 because it is both an act of self-improvement and something “slightly nice” (love that phrase).

2.0, for those of you who haven’t been following us, is a rather dramatic overhaul of the way we do business. It’s about streamlining the way we work in a way that places added emphasis on speed, partnerships and patients.

CIRM 2.0 makes it easier for both companies and academic researchers with promising projects to partner with CIRM to get the support they need when they need it, reducing the time from application to funding from around two years to just 120 days – that’s the “self-improvement”.

In a news release marking the launch of 2.0, our President and CEO Randy Mills summed up the reason why we are making these changes:

“Our mission is to accelerate the development of stem cell therapies for patients with unmet medical needs. Today, in officially launching the first three programs under CIRM 2.0, we have boldly reaffirmed our commitment to continuously seek new and innovative ways to better serve that mission.”

Simply put, we hope that by improving the way we work we can help speed up the development of treatments for patients in need. I would say that more than qualifies as being “slightly nice.”

You can hear Randy talking about CIRM 2.0 here

This is just the first phase of our new look. In December our governing Board gave us $50 million to get this up and running for clinical stage work over the next six months (you can find links to the Program Announcements for that work on our news release). Later this year we are going to expand 2.0 to include both discovery – or basic – research and translational research.

We are now in our 11th year as an agency funding stem cell research. Last year was a big year for us with 8 projects we are funding approved for clinical trials. But as we see every New Year, getting a little older shouldn’t stop you from wanting to improve or making the next year or years even better. Or from just doing something “slightly nice” for others.