Stem Cell Stories that Caught our Eye: Lasers Regenerate Dental Tissue, European Commission Rejects Stem Cell Ban

Here are a couple of 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 for fun.

Laser therapy spurs stem cells to repair teeth. Harvard University scientists have, for the first time, used a type of laser trigger to coax stem cells to regenerate dental tissue. As reported this week in the journal Science Translational Medicine, the research team—led by Harvard Bioengineer Dr. David J. Mooney—sets the stage for one day harnessing this therapy to regenerate many types of tissue.

Specifically, Mooney and his team used a low-power laser to trigger dental stem cells to grow into dentin—the layer of tissue encased inside the tooth enamel that makes up the majority of the tooth. Scientists have used a variety of methods to get these stem cells to grow dentin, with limited success. But as Mooney explained in this week’s news release, the team took a different approach:

“Our treatment modality does not introduce anything new to the body, and lasers are routinely used in medicine and dentistry, so the barriers to clinical translation are low.”

These studies were performed first in animal models and then in human dental tissue in a dish. Next, the team plans to start human clinical trials. If their principle proves successful, Mooney is optimistic that this technique could be applied to a variety of cell types.

European Commission Votes No on Stem Cell Ban. In a move hailed by scientists in Europe and around the world, the European Commission has rejected a request by the organization One of Us to ban funding for human embryonic stem cell research.

One of Us filed their petition, which had garnered 1.7 million signatures, with the Commission’s new European Citizens’ Initiative scheme. This scheme was launched to boost participatory democracy throughout the European Union. As a rule, any petition with at least 1 million signatures automatically triggers a parliamentary hearing and formal response from the Commission.

As reported in Nature News, the Commission’s reasoning for rejecting the petition was as follows:

“It said that the EU Council of Member States and the European Parliament had last year debated the issue thoroughly, and no new information was available to warrant a return to the debate so soon. At the time, member states and parliament both agreed that stem-cell research held great promise for currently incurable diseases such as Parkinson’s disease, and it was thus in the public interest to support it. They also agreed that human embryonic stem cells are still sometimes required in such research.”

In fact, support for human embryonic stem cell (hESC) research has been steadily increasing around the world, including back here at home. A Gallup poll published today showed that 65% of Americans support hESC research—a record high.

A Second Chance for a Spinal Cord Injury Trial, and a Powerful Reminder from Patient Advocates

Yesterday’s meeting of our governing Board was important for a number of reasons. First, the Board voted to invest some $32 million to try and get two promising projects into clinical trials – more on that in a minute – and also to try and attract some world-class researchers to California through our Research Leadership awards. It was also the first Board meeting for our new President, C. Randal Mills, Ph.D.

However, for me one of the most important parts of it was that it offered patient advocates a chance to come and talk to the Board directly, to share with them their hopes for stem cell research, and their needs in battling disabling conditions.

Yesterday a mother, Silvia Michelazzi, who suffered preeclampsia during her pregnancy and almost lost her child talked about the need for research to find better ways of preventing this deadly condition. Silvia’s daughter was born at 29 weeks and spent the first couple of months of life in a hospital neonatal intensive care unit.

One of the researchers we are funding, Dr. Mana Parast of UC San Diego, is doing some fascinating work in using iPS cells to better understand how preeclampsia works, and hopefully to find better ways of preventing it or treating it when it’s detected. We’ll be posting video of both talks in the next few weeks.

Earlier a group of individuals who have Parkinson’s disease talked to the Board about what it is like to live with that disease, to slowly lose control over their bodies and know that it was only going to get worse. They made a strong plea for more funding for stem cell research into this area.

To hear people like this speak is a powerful reminder of why we do this work; it puts a human face on the need for more research into so many areas, and why we need to do all that we can to accelerate that research, to find new treatments and cures.

Too often patients are left out of the discussion when it comes to funding research. At the stem cell agency we invite them into the room and welcome hearing from them. It’s not always easy to listen to what they have to say, particularly as we know some research is at an early stage of development and we won’t always be able to do what they want us to. But those voices are an important part of what this agency is all about. We were created by the people of California, so it’s important that the people feel they can come and talk to us any time they want.

From a business perspective yesterday’s meeting was very productive. The Board voted to invest $14.3 million in Asterias Biotherapeutics to move a stem cell therapy for spinal cord injury into clinical trials. This is the second time this approach will have been tried. The first was with Geron in 2010 and that trial, even though it ended earlier than expected because of financial reasons, showed the approach appears to be safe. Asterias is going to take it to the next level.

The other big award was $5.6 million to John Zaia at the City of Hope near Los Angeles to move his work in finding a treatment for HIV/AIDS into clinical trials.

Both are part of our Strategic Partnership program that requires them to provide matching funds for this work.

You can read all about those awards and the Research Leadership ones too in a news release we issued after the meeting.

kevin mccormack

Stem Cell Agency Governing Board’s Meeting is Now Live

The May Board meeting is now underway. Big items under discussion today are funding for our Strategic Partnership Awards – designed to encourage more partnerships with industry – and Research Leadership – to attract the best stem cell scientists to California.

You can listen in to the proceedings in a number of different ways.

 PHONE:
 Dial in Information
Dial In: (866) 233-3841
Access Code: 327811

 ONLINE
WebEx Link
1. Go to https://cirm.webex.com/cirm/onstage/g.php?MTID=e9cb35b652343bba81687d2e7…
2. Click “Join Now”.

AUDIO CAST
 To access the live event or archive, use this URL:
https://im.csgsystems.com/cgi-bin/confCast
 Enter Conference ID# 327811
Then click Go.

We will be issuing a news release at the end of the funding decisions and will post a blog update on the meeting tomorrow

Kim Kardashian and C.C. Sabathia—Stem Celebrities: Raising Awareness or Raising the Risk?

One of the easiest, and most shameless, ways of getting attention on social media is to drop celebrity names into the mix. So when you see that this blog includes references to both Kim Kardashian and Yankee’s baseball pitcher C. C. Sabathia you might conclude that that is what I’m trying to do.

A reasonable assumption, but happily a wrong one.

No, I mention these two high profile figures because they are stem celebrities; famous people who are making news because of their use of stem cells.

Kardashian is a fan of the stem cell facial

Kardashian is a fan of the stem cell facial

In the case of Ms. Kardashian (now Mrs. Kanye West), she prepared for her weekend nuptials by getting what US Magazine calls a “$500 stem cell facial”. The magazine goes on to describe the procedure as a “famed vegan stem cell serum,” which uses stem cells from a “marine plant, which are thought to firm and lift the skin.”

I would never suggest that Ms. Kardashian is wasting her $500 but there is no evidence that plant-based stem cells can actually achieve the results being attributed to them. But don’t take my word for it. Here’s what Dr. Ronald L. Moy, a cosmetic and plastic surgeon in Los Angeles, and the former President of the American Academy of Dermatology, had to say in an interview in FabFitFun (and I have to admit, I had a lot of fun researching this piece):

“While there’s evidence that human stem cells, when harnessed with growth factors, stimulate epidermal stem cells to thicken the skin, which leads to tightening, there’s no scientific evidence that plant-stem-cell growth factors work in the same way. After all, how could a plant cell have any effect on human skin?” 

Ms. Kardashian just wanted to look her best on her wedding day, and who would blame her. Yankee’s star C. C. Sabathia, on the other hand, wants more than to just look good on the pitcher’s mound, he wants to dominate the opposing team’s lineup. A recent injury to his knee is threatening that and so he has been getting cortisone shots and a stem cell injection.

It’s not clear what kind of stem cells Sabathia is getting, or how many and how often, but what is clear is that there are no clinical trials that show this kind of therapy is effective. In time we may learn that the use of certain stem cells may have an anti-inflammatory impact on knee injuries, or even – in the Holy Grail of some approaches – help restore damaged tissues and cartilage. But right now, we just don’t have any evidence to show that this kind of approach is both safe and effective.

The bulk of the danger with stories like these is not that the individuals involved are likely to be harmed (though they may be) but that the attention their famous names draw to stem cell therapies could lead others to copy their example, and undergo procedures for which there is no evidence to show they are safe and effective.

Like it or not, celebrities have a big impact on our behavior. A study published in The Journal of Pediatrics last year looked at 181 children in the UK and found that these kids ate more potato chips after watching TV ads that featured a well-known sports figure. If celebrities can help market potato chips, there’s no reason to believe they can’t also help market stem cells being sold as therapies.

Stem cells have extraordinary potential. Over the years supporters of stem cell research have been accused of hyping that potential, making claims that could not be met. We at the stem cell agency have worked hard to be level-headed and realistic in the way we talk about the research and the great progress that is being made.

The danger with stem celebrities is that their fame will drown that out and lead people to go in pursuit of very expensive treatments that don’t actually treat anything. Without adequate safety testing, these treatments may instead cause harm.

We have written a lot about this in the past, and doubtless will write more in the future as more and more clinics open up offering these unproven remedies. Here are a couple of excellent resources to go for information on the process of turning stem cells into therapies, and on stem cell tourism, traveling to other countries to get unproven therapies not available here.

Write your Ticket to the Stem Cell Science Event of the Year

For many stem cell scientists one of the highlights of the year is going to the annual International Society for Stem Cell Research (ISSCR) conference. It’s like Disneyland for researchers. This year the event is being held in Vancouver, Canada. But many younger scientists won’t be going because they can’t afford it. So UC Davis researcher and avid blogger Paul Knoepfler has teamed up with ISSCR to help one lucky scientist go. Here’s Paul’s guest blog explaining how they can apply:

What’s better than a four-day stem cell meeting held in beautiful Vancouver, B.C. that includes all of the newest and most cutting edge research?

If, like me, you are a lover of all things stem cell your first impulse may be to shout out “nothing!” and I am betting you will already know that I am talking about the ISSCR Annual Meeting being held this year in that fantastic locale.

Beautiful Vancouver, British Columbia home to this year’s ISSCR Annual Meeting

Beautiful Vancouver, British Columbia home to this year’s ISSCR Annual Meeting

However, the answer I had in mind is that the only thing better than going to ISSCR is getting to go to that meeting for free.

How do you get to that stem cell happy place?

I have teamed up with ISSCR to run a contest with the prize being free registration to the ISSCR meeting that runs from June 18-21.

All you have to do is write a short essay addressing this topic: why do I want to go to ISSCR 2014?

The winner gets free registration and their essay gets published on my blog to be read by the stem cell community.

For a few additional rules and details, check out the announcement of the contest here.

The deadline for entries is Friday May 30th. The winner will be announced on Monday June 2nd.

What am I looking for in a winning essay? As a stem cell researcher and writer myself, I am hoping to get entries that are clever, creative essays that convey genuine, interesting reasons for wanting to go to this great meeting. You will have to be concise too because the limit on length is a strict 300 words.

There may be additional entries published on my blog if more than one really wows me, and other perks like stem cell swag for entrants could come into play depending on the number of entrants and the quality of their writings.

So start brainstorming and writing and then send your entries to me at knoepfler@ucdavis.edu.

I hope to see you in Vancouver.

Paul Knoepfler 

Stem Cell Stories that Caught our Eye: Safety of First Embryonic Cell Trial, Engineered Organs, New Hips

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.

Update on status of bioengineered organs. Kevin Mayer, writing for Genetic Engineering & Biotechnology News, this week produced the best lay overview I have read on bioengineered organs. Under the heading “bioficial organs” he covers the many ways to create scaffolds that can hold stem cells to create organs. He recounts the successes to date crafting simple organs like the trachea, bladder, vagina or nostril. He talks about the possibilities and limitations of using 3D printing to scale up production of those organs, and delves into recent reports of creating organ-like tissue on chips to be used for disease modeling and drug screening. CIRM covered many of these same topics in our workshop on Opportunities and Challenges for Tissue Repair and Regeneration.

First embryonic stem cell trial called safe. Data from the first-in-human clinical trial of cells derived from embryonic stem cells suggest the stem cell infusions were safe. The data provide welcome news to the field as a whole and hope for the million-plus Americans living with spinal cord injury, the focus of the trial. The biotech company Asterias reported the data at the American Society for Gene and Cell Therapy Thursday. The firm had bought the stem cell assets of Geron, the company that had begun the trial in 2010. In the five patients, all followed for two to three years, the team found no evidence of any ill effects from the stem cell infusion. Also, even though the researchers stopped all immune suppressants 60 days after transplant, they saw no sign of an immune response to the donor cells. TMCnews carried the company’s press release.

CIRM had provided funding for the initial Geron trial, but the company returned the award when they decided to discontinue the trial due to financial considerations. We continue to fund work in the field, which you can read about on our spinal cord injury fact sheet.

Creating mature nerve cells better mimics disease. Many teams have reported creating disease-specific nerves in the lab by creating iPS type stem cells from the skin of patients with neural diseases like Alzheimer’s, but they are less than perfect models of the disease. While they mimic the disease better than any animal model, the nerves resemble those of a newborn, not an older person likely to get the disease. Now a team at the University of Cambridge in the U.K. has developed a process that tricks the maturing iPS stem cells into continuing down the maturation pathway. The result is nerves in a dish that behave more like those in the patient. The website PhysOrg ran a story about the work that is to be published in the May 27th journal Development.

3D printing combined with stem cells for new hip. Deterioration around the site of the hip joint often results in less than optimal results when an artificial hip replaces the bad joint. Another problem is that off-the-shelf sized joints, just like shoes, don’t always fit perfectly. So, a team at the University of Southampton in the UK has developed a one-two-punch to create a better hip. First they used a 3D printer to create a hip and socket that exactly match the patient’s and then they created a bone graft with stem cells to create stronger and better fitting bone behind the socket. The web portal HealthCanal ran the university’s press release.

Ground beef made in the lab. There was a lot of silliness on the web this week about using stem cells to grow hamburgers in the lab. But Popular Science did a good old-fashioned explainer about the actual science behind the concept.

Don Gibbons

Slowing Down the Clock on Aging Hearts

It’s like something from a nightmare: a disease that ages you at a breakneck pace, so that by age 12, your body more closely resembles someone in their 80’s—inside and out.

Instead of enjoying your childhood and adolescence, you suffer from diseases usually reserved for octogenarians: including heart disease, kidney failure and stroke.

Chances are, you won’t make it past your 13th birthday.

However fantastical this may seem, this condition is real. Called progeria, this rare genetic disorder affects only about 100 people worldwide. But with the help of the latest stem cell technology, a few determined scientists are speeding towards a cure.

In the May 19 issue of the Proceedings of the National Academy of Sciences, University of Maryland researchers have uncovered what may be driving the accelerated aging process. Specifically, the team identified a toxic protein that wreaks havoc on the patient’s arteries from a young age—thereby priming the young patient for disease.

The study’s senior author, Dr. Kan Cao, says in a recent news release that these findings offer hope not just for progeria patients and their families, but also for anyone suffering from or at risk of developing age-related diseases:

“This gives us a very good model for testing drugs to treat progeria. And it may help us understand how cardiovascular disease develops in people aging normally.”

Scientists have long known that progeria was caused by a genetic change, or mutation, that results in the production of a faulty version of a protein called progerin. But until now, they have been unable to pin down precisely how this faulty protein leads to progeria’s deadly symptoms.

Seen through a microscope, these color-enhanced skin cells from progeria patients have been induced to become smooth muscle cells, some with abnormalities such as double nuclei. [Credit: Haoyue Zhang]

Seen through a microscope, these color-enhanced skin cells from progeria patients have been induced to become smooth muscle cells, some with abnormalities such as double nuclei. [Credit: Haoyue Zhang]


Confounding the efforts, progeria has been extremely difficult to study, in large part because of the frailty of the patients. The disease most seriously affects the patient’s internal organs, but obtaining tissue samples is not generally possible, as the procedure is far too invasive. So Dr. Cao and her team tried a different approach.

They took skin samples from progeria patients and, using induced pluripotent stem cell (iPS cell) technology, transformed them into smooth muscle cells. Smooth muscle cells are a type of cell that lines the walls of blood vessels and other tissues. In this case, these smooth muscle cells were genetically identical to the patients’ native muscle cells, effectively allowing the researchers to model the disease in a dish over time, cell by cell. And when they did so, they solved a big part of the riddle.

The faulty version of progerin, the team realized, was interfering with a process essential the health and well being of cells: DNA repair.

As cells grow, age and divide, the DNA housed within them can sometimes break. When this happens, a protein called PARP-1 senses this break and, like a molecular handyman, repairs the damage. But in the case of progeria, the faulty progerin protein builds up within the cells. As it does so, PARP-1 levels drop. Without the expertise of PARP-1, the cells are unable to correctly repair DNA breaks. Sometimes they get it right, but usually they get it wrong. And when the cells try to divide, they can’t. Some end up as one cell with two nuclei, while others end up killing themselves in an act called “mitotic catastrophe.”

Cao and her team reasoned that people with progeria, who are losing smooth muscle cells much faster than is normal, are more vulnerable to stresses, such as blood pressure, which then increases their likelihood of heart disease and stroke.

CIRM-funded researchers at the Salk Institute reported a similar finding in 2011, when they derived muscle cells from iPS cells made from a patient with a different form of progeria. In our 2011 blog post about that work, the Salk team found that lamin A, a protein that accumulates in the normal aging process, also builds up in patients suffering from this form of progeria.

The next step for Cao’s team, she says, will be to find out the nature of the relationship between progerin and PARP-1. She also hopes to use iPS cell technology to test potential treatments for the disease. Since beginning her work on progeria, Cao has become close with progeria patients, and their families. It is these relationships that have spurred Cao and her young research team to understand the disease—and to find a cure:

“[My] students began thinking, ‘My research is so important for the families.’ It’s a lot of motivation for them. And a lot of pressure for all of us to work quickly.”

Getting at the Root of Cancer: Cancer Stem Cells Tracked down in Human Patients

The backers of the cancer stem cell hypothesis just got a boost from scientists at the University of Oxford, UK, and the Karolinska Institute in Sweden, who last week used an advanced genetic tracking technique that identified, in patients, the presence of cancer stem cells—a small subset of cancer cells that many experts view as the underlying cause of cancer.

Scientists have long searched for a reliable way to measure and track cancer stem cells.

Scientists have long searched for a reliable way to measure and track cancer stem cells.

The concept of cancer stem cells has gained traction in recent years, but remains a controversial topic—in large part because it has proven difficult to definitively isolate them. Scientists have theorized that a small cadre of stem cells is responsible for propagating the growth of a patient’s cancer. So, even if the most advanced cancer treatments can destroy the tumor itself, there is always the risk of resurgence—unless the cancer stem cells are destroyed too.

As Dr. Peter Woll, the study’s first author, explained in last week’s news release:

“It’s like having dandelions in your yard. You can pull out as many as you want but if you don’t get the roots they’ll come back.”

As a result, considerable effort has been made worldwide to try track down these cells in their natural environment—because if they can be found, they could also be destroyed, thus destroying the cancer.

In this study, published last week in the journal Cancer Cell, the researchers studied patients who suffered from myelodysplastic syndrome (MDS), a blood condition that often progresses to acute myeloid leukemia. Using genetic tools, the researchers pinpointed specific cancer-driving mutations in the DNA of the tumor cells. Working backward, the team was then able to identify a small subset of cancer cells that had the hallmark properties of the elusive cancer stem cells. As explained in the news release:

“The MDS (cancer stem) cells were rare, sat at the top of the hierarchy of MDS cells, could sustain themselves, replenish the other MDS cells and were the origin of all stable DNA changes and mutations that drove the progression of the disease.”

Woll argues that these findings offer “conclusive evidence for the existence of cancer stem cells” in patients with MDS. The implications of this discovery, Dr. Woll argues, offer new insight into permanently eliminating a patient’s cancer:

“It is a vitally important step because it suggests that if you want to cure patients, you would need to target and remove these cells at the root of the cancer—but that would be sufficient, that would do it…. [These findings] give us a target for development of more efficient and cancer stem cell-specific therapies to eliminate the cancer.”

How are CIRM-funded scientists tackling leukemia? Find out at our Leukemia Fact Sheet.

Anne Holden

Beautiful by design: turning a stem cell research workplace into a work of art

Broad Center for Regenerative Medicine & Stem Cell Research, USC

Sometimes what seems like an interesting project, a fun thing to try out, turns out to be a great idea, one that has the power to completely transform the way others see what you do and where you do it. That’s what is happening at the Broad Center for Regenerative Medicine and Stem Cell Research at the University of Southern California (USC).

A few weeks ago I told you how USC is using art to break down barriers, bringing together students studying art and design with stem cell researchers to collaborate on a project to come up with a new way of communicating about stem cells. The end results are far beyond what they had hoped for.

First, the art students toured the research facility, talked to the scientists and fell in love with the science. In a portfolio put together by the students they said they were “inspired by the imagery and research process.”

Then they got to work, coming up with ways of incorporating the imagery from stem cell research into the actual building itself. The students said they were inspired by the way the researchers worked together, and how the building itself seemed to promote that kind of collaboration because of its design. So, they set out to mirror that idea of collaboration by creating:

 “a designed environment that would enliven the space, enrich the researchers’ experience, convey a sense of the current research to visitors, and be visually energizing and engaging.”

They came up with a number of different proposals using different stem cell images and colors to brighten up the building and help give visual clues as to where you are in the facility. They wanted those colors and images to be part of the experience from the moment you walked in the lobby, to getting out of the elevator and walking down a corridor.

The end design will not just engage the eye but also the mind, using quotes from scientists, writers and patients to inspire people to think, to hope, and to reflect on the role that science plays in all our lives. One they have in mind comes from science fiction writer Ray Bradbury:

“The best scientist is open to experience and begins with romance – the idea that anything is possible.”

Although the semester is almost over the students have asked if they can stay on over the summer, to help see the final designs implemented.

At USC they’re showing that an open mind and a vivid imagination can turn a work place into a work of art. The science inspired that art. Now the hope is that the art will inspire the science.

kevin mccormack

Stem cell stories that caught our eye: stroke, growing bladder tissue and a clinical trial roundup

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.

Early data on stem cells for stroke promising. The British company ReNeuron reported preliminary data on its clinical trial in stroke patients at the European Stroke Conference in Nice last week. In an article in the New Scientist the CEO of the company gave an appropriately cautious assessment: “we are seeing what seems to be a general trend towards improvement.” The data represented only 11 patients, but they were chosen well. They were all at least six month out from their stroke, the generally accepted outer limit of time when neurologist expect any spontaneous improvement. They measured five indicators of neurologic health and while they saw some improvement in all of them, the greatest gain was on the measure of quality of life, which increased by an average of 40 percent. You can read about CIRM-funded projects in the field on our stroke fact page.

From skin to stem cell to bladder tissue. While Tony Atala at Wake Forest has fashioned replacement bladders for several children using scaffolds and adult cells, researchers had not succeeded in coaxing pluripotent stem cells into becoming viable bladder tissue. A team at the University of California, Davis has now reported that achievement in Stem Cells Translational Medicine, the journal Tony edits and CIRM helped to found. They started with iPS type reprogramed stem cells that could theoretically be made from any patient and provide them with new bladders that matched their own genetics. Such replacement bladders might not have some of the limitations of those made at Wake Forest. The Davis team’s success came through an elaborately develop protocol to prod the stem cells into becoming the desired tissues. The Davis Enterprise reported on the work.

Therapies reaching patients. Brad Fikes, who clearly enjoys writing about biotechnology for the San Diego Union Tribune, did a nice roundup on stem cell research reaching clinical trials. He noted that the master registry for these human tests, clinicaltrials.gov, lists 774 stem cell trials, with 147 of those taking place in California. In particular, he wrote about a spinal cord injury trial scheduled to begin this fall at the University of California, San Diego. He described that trial’s use of a specially designed device that delivers precisely targeted micro-injections of cells to the site of the injury. A trial CIRM is funding to begin within the next year or so will use the same device to try to treat amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. Brad also devoted a fair amount of ink to describe the use of mesenchymal stem cells found in bone marrow and fat. The experts he quoted did a good job of explaining that most of the therapeutic potential of these cells comes from their ability to modulate our immune response.

Multiple disciplines needed to develop therapies. A scientist from Charles River Labs contributed an opinion piece in The Scientist that made a good case for the value of building project teams that use people with very different perspectives. She noted that no team from a single institution is likely to have all the expertise in the science, regulatory issue and manufacturing scale up to bring a product to market. She noted that CIRM actively works with its research teams to educate them about the full continuum of activities needed to move stem cell research from the research bench to routine patient care. One example is the Critical Path Workshop that we organize at our periodic all-grantee meetings.

Don Gibbons