Remembrance of things past – how some stem cells remember what they used to be

Can you tell the difference? Embryonic (left) and iPS cells side by side

First there were embryonic stem cells. Then came induced pluripotent stem (iPS) cells, which start out as adult cells, such as skin cells. Using a variety of methods, scientists can turn these adult cells into iPS cells, which can then be changed or turned into any kind of tissue, just as embryonic stem cells can.

These iPS cells offer advantages over their embryonic cousins. In theory, transplant tissue could be created from a patient’s own cells, reducing the risk of an immune response such as often happens after a kidney or liver transplant. It’s a neat idea, but we have to learn more about iPS cells to make it work. In particular, we need to figure out the differences between induced pluripotent and embryonic stem cells.

Ideally, iPS cells would be a clean slate, retaining no evidence they’d ever even been an adult cell. But scientists have long known that iPS cells retain a certain amount of “memory” from their former lives as adult cells.

Now, CIRM-funded researchers at UCLA, and elsewhere, have published a study in Stem Cell Reports that identifies some important differences between embryonic stem and iPS cells. They focused on a process called methylation, in which molecules called methyl groups attach to DNA to silence a gene. Methylation is a sub-discipline of epigenetics, which studies how genes get turned on and off.

Methylation is a big deal because, as our bodies develop, some genes become unnecessary and need to be silenced, while other genes have to step up and orchestrate the next job. The researchers wanted to know whether methylation patterns were different between iPS and embryonic stem cells. Turns out they are.

The study found that, quite often, iPS cells retain old methylation patterns from when they were adults, remembrance of things past. Some genes were even more methylated than usual—hypermethylated—when compared to either embryonic stem cells or fully formed adult cells. Apparently, the process of reprogramming adult cells to stem cells changes their methylation profiles, turning off genes associated with immunity and cellular housekeeping.

This new information provides researchers a series of biomarkers to distinguish between embryonic and induced pluripotent stem cells. In addition, illuminating how this important mechanism differs in iPS cells could make them more useful in the long run.

Josh Baxt

Genomics award advances the field and catches the attention of the media

One of the most amazing parts of working at the stem cell agency is being part of an organization that is helping chart a whole new approach to treating disease and is breaking new ground in the ways it does that. Yesterday’s Board meeting was a perfect example.

Our governing Board, the Independent Citizens Oversight Committee (ICOC), voted to approve $40 million in funding to create a new Center of Excellence in Stem Cell Genomics. It’s a program that will bring together the fields of genomics and stem cell research. The goal is to use genetic analysis to better understand what happens in a particular disease and to come up with new ways to treat it, ways that can potentially be tailored to meet the needs of individual patients.

In a news release announcing the funding our President, Alan Trounson Ph.D., said;

“This Center of Excellence in Stem Cell Genomics shows why we are considered one of the global leaders in stem cell research. Bringing together this team, to do this kind of work means we will be better able to understand how stem cells change as they grow and become different kinds of cells. 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.”

We were understandably excited by the news. So too were the members of the winning consortium headed by Stanford but including researchers from the Salk Institute, UC San Diego, Scripps, the J. Craig Venter Institute, Illumina and UC Santa Cruz. Reporters from newspapers, radio, TV and online news outlets around the state seemed to also appreciate the significance of the award.

The story was carried in outlets from the Sacramento Bee and San Francisco Chronicle to the San Diego Union Tribune. ABC7 TV in San Francisco covered the meeting and NPR stations around the state also aired pieces about it. It even caught the interest of the sometimes-jaded scientific business press.

The money we use to fund this research comes from the people of California, thanks to Proposition 71, so it’s important that they know how we are spending their money. This round of stories showed them it’s being used in ways that could one day help change the face of medicine.

On a lighter note the Board meeting also welcome two new members, Lauren Miller as the Patient Advocate for Alzheimer’s disease, and Joe Panetta as the representative for the biotech industry. It was a great meeting for them to make their debut.

kevin mccormack

You won’t be bored at our Board meeting

When most people think of Board meetings the usual image is of a fairly dry, business-focused talk around a big table. Clearly those people have never been to a meeting of our Board, the Independent Citizens Oversight Committee (ICOC).

They are never dry, or dull, and today’s Board meeting is likely to be even livelier than usual. That’s not too surprising. Any time you put $80 million up for grabs you are bound to generate some interest, even excitement, among researchers.

Up to $40 million of that total is focused on creating a Centers of Excellence in Stem Cell Genomics, a completely new approach to stem cell research that brings together genomics – the study of the complete genetic make-up of a cell – with stem cell research. The goal is to use these tools to gain a deeper understanding of the disease processes and ultimately to find safer and more effective ways of using stem cells in medical research and therapy.

The other $40 million is for Basic Biology. These awards go to researchers trying to advance the field by tackling significant, unresolved issues in human stem cell biology.

There’s a lot at stake, and it’s bound to provoke a fascinating discussion. And you can hear it all live. There are a number of options for listening in or following the meeting either by phone or online. Here they are:

Dial Information:Dial In Number: (866) 254-5935 Confirmation Number: 317421

Audio Cast:
To access the live event or archive, use this URL: https://im.csgsystems.com/cgi-bin/confCast
Enter Conference ID# 317421. Then click Go.  

WebEx Info
To join the event as an attendee go to
https://cirm.webex.com/cirm/onstage/g.php?d=805281818&t=a&EA=acheung%40c… 
2. Click “Join Now“.

And of course if you can’t make the meeting we’ll bring you all the highlights in our blog tomorrow.

kevin mcormack

A view from the inside: one person’s perspective on the stem cell agency

On the first Monday of every month the stem cell agency staff all gather to talk about some of the most pressing issues facing us. It’s a chance to share information and exchange ideas. At a recent meeting one of our legal team, Cynthia Schaffer, used the occasion as the inspiration for this blog.

 It is a Monday morning staff meeting. As I look around the room at my colleagues I think – “why do they choose to work at CIRM?” For most the answer is NOT “the money”. After all, CIRM is a State Agency.

I believe that the majority would answer the same way I would- that they work at CIRM because they believe in the cause – pioneering a new therapeutic paradigm to help those suffering from illness.

Out of the almost 60 employees, the largest section of staff are PhD and MD Scientists with backgrounds in academia and industry. We don‘t have much turn-over in these positions. The scientists come to CIRM and they stay. They are dedicated employees in spite of the punishing calendar of new rounds of funding, the constant progress reports that need to be filed on existing research we have funded, plus grant reviews and a myriad of other deadlines.

The next largest group at CIRM is the grant managers who make sure the payments go out and the reports come in – we need to keep a good accounting of all the work we are funding to show that it is being done on time and meets the goals laid out for it.

Then there is the grants review team. They are constantly checking conflicts, finding experts to sit on Grants Working Group panels (these are the independent experts who review all applications for funding) and answering questions from applicants.

We have a strong business development team who are out touting CIRM’s 70+ portfolio of research programs. These will need additional funds to get through the strict regulatory process before they are widely available to public. We fund the early phase clinical trials – where they are taken out of the lab and tested in people – but these projects will need additional funding from either a big pharmaceutical company or venture capitalists, to get them to the final phase of the approvals process, a Phase 3 clinical trial.

CIRM’s communications staff tells the agency’s story everyday – how the science is progressing, engaging with the public to let them know how their money is pushing the boundaries of science, and engaging with the patient advocate community to make sure their voices are always a part of the conversation.

Beyond that, we have attorneys and accountants and computer people (who doesn’t?). I am in this last group of administrative staff who wear many hats and fill in many gaps.

I’m sure I don’t need to mention the agency’s senior leadership or the dedicated CIRM Board of 29 who are already the busiest people (Heads of Medical Schools, Chief Executive Officers of Health Care Systems) and yet the find the time to spend a minimum of 80 hours attending our Board Meetings and then spend double that amount of time reading the mountains of materials that CIRM provides in advance of the meetings so that the Board Members can be informed and productive.

However, as great as the CIRM staff is, both as individuals and as a group, CIRM will be judged by what it has accomplished. My personal answer to that is philosophical – where would the cell therapy field be without CIRM having jump-started it?

Do we care about getting credit or getting things done? To quote President Harry S. Truman – “It is amazing what you can accomplish if you do not care who gets the credit.” So, CIRM’s amazing staff keeps plugging along and I am filled with pride as I look around the room at the staff meeting because I work side by side with dedicated professionals on a mission to make the world a better place.

Cynthia Schaffer

Chris Furbee’s Autobiographical Huntington’s disease film wins Slamdance Film Fest Award

Huntington’s Dance interview subject Gene Furbee (L) and film director Chris Furbee

Did you hear that loud cheer last Friday morning? Maybe your floor shook a little bit? That was the CIRM staff celebrating a big win for Huntington’s disease (HD) patient advocate Chris Furbee and the HD community in general.

This past week, Chris’ autobiographical film “Huntington’s Dance” won the 2014 Slamdance Jury Special Mention for Most Compelling Personal Journey. You can watch a trailer of the movie on YouTube. And here’s a short synopsis of the movie from the Slamdance website:

The story of one man’s reckoning with his family’s brutal, hereditary disease: Huntington’s Disease. This first person account brings the viewer intimately into their lives. We see his denial, his mother’s death, his grappling with being tested and his eventual diagnosis. His path from caretaker, to victim to activist is tracked in a unique diary fashion over the course of 18 years.

I first met Chris in 2010 when we featured him in our short video about Huntington’s and stem cell research. In the midst of that video interview, I learned that he himself was a filmmaker and he showed me some clips of the documentary that he hoped to eventually finish and get financed.

So it was exciting enough to blog two weeks ago about the completed film’s acceptance into the top-rate Slamdance film festival that runs in parallel with the Sundance Film Festival in Park City, Utah. Now I’m over-the-moon to learn of this jury prize.

Congratulations Chris for achieving recognition for an 18 year journey to tell your story and raise awareness about Huntingon’s disease!

To learn about CIRM-funded stem cell research related to Huntington’s disease, visit our HD fact sheet.

Todd Dubnicoff

Stem cell stories that caught our eye: blindness, targeting cancer and science literacy

Researchers have used stem cells to help retinal cells like these grow the blood vessels they need.

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.

iPS stem cells from cord blood for retina repair. A team at Johns Hopkins has moved reprogrammed stem cells, so called iPS cells, closer to clinical use via a couple different steps. While you can use the iPS technique to reprogram any adult cell, they chose the cells in umbilical cord blood, which being so young have fewer of the mutations that tend to accumulate in our cells as we age. So, these cells may be safer or at least more uniform. The team also perfected a technique they had reported earlier that used molecular mechanisms instead of viruses to carry out the reprogramming. Most important, they found that when they matured those stem cells to become precursors of blood vessels, they could be injected into mice with damaged retinas and succeed in growing needed new vessels.

The research was published in the journal Circulation and written about on the web site science 2.0. You can read about work CIRM funds in the area on our blindness fact sheet.

Stem cells carry chemo to cancer. Since stem cells naturally home to inflammation and stem cells view cancer as inflammation several teams have begun efforts to use stem cells to carry cancer-killing agents to tumors. CIRM funds a team using donor neural stem cells to target a deadly brain cancer. Now a German company apceth (applied cell therapy) is using a patient’s own bone marrow stem cells to target gastro-intestinal tumors. The release from the company run by B3Cnewswire makes it clear they are using the type of stem cell in bone marrow called mesenchymal cells. But it does not clarify how they have altered those cells to deliver a deadly punch when they arrive at the tumor. It does indicate that the therapeutic impact is through genetic manipulation of the cells that can be activated selectively after the cells have traveled through the blood stream and arrived at the tumor.

Stem cell patent questioned. For stem cell wonks who watch some of the insider baseball in the field, Science news reporter Eliot Marshall has written a good review of the arguments on both sides of the court case determining the validity of the patents underlying embryonic stem cell technology. Spurred by the Supreme Court’s decision last year that human genes cannot be patented, the advocacy group Consumer Watchdog challenged the patents held by the University of Wisconsin’s alumni foundation. While I am not going to take sides here, there are clearly argument on both sides of this and it is rare to get them laid out as well as Eliot has, something I have come to expect from him over the years.

Science reporting needs a boost. I love it when a big name takes up one of my soap boxes, in this case the lack of science literacy in this country and how the shrinking number of science journalists is adding to the problem. Renowned medical ethicist Arthur Caplan detailed the issue in an interview published in The Chronicle of Higher Education and About.com ran a review of the piece. It has a great quote from Caplan:

Children are not going to flourish at science in a society that treats it either as something you can believe in selectively, something that is simply one point of view, or something about which anyone can have a credible opinion no matter how ill-qualified, dumb, or misinformed.

He goes on to describe the damage done by cutbacks of dedicated science journalists in news rooms and hits another hobby horse of mine: scientists have a responsibility to communicate their work to the public. I hope a few publishers read his remarks, and a few scientists, too.

Don Gibbons

Hanging out after the Hangout – how a talk about a new treatment for type 1 diabetes sparked a deeper conversation

You know you have hit on an important topic when the conversation continues long after you expected it to end. That’s certainly what happened with yesterday’s Google Hangout on Diabetes that we hosted. While the Hangout itself was, I thought, engaging and informative, it clearly only began to touch on the full scope of the issue.

After the Hangout ended I thanked the four experts who made up our panel – Drs. Kevin D’Amour and Howard Foyt from ViaCyte, Dr. Francisco Prieto a physician and researcher and the Patient Advocate for Diabetes for our governing Board, and Chris Stiehl, who has been living with type 1 diabetes for 54 years – and that began a conversation about all the different aspects of the disease that we simply didn’t have time to touch on during the Hangout.

While the Hangout focused on treatments and therapies for the physical side of diabetes, part of the post-Hangout conversation focused on other aspects. Chris pointed out:

 “I believe one of the major issues in diabetes is the psychological aspect of the disease, public ignorance and discrimination, etc. I know that CIRM does not fund that kind of research, but diabetes depression is a key component of who survives and who doesn’t” 

Francisco responded to that by broadening the conversation even wider:

 “I agree Chris that the psychological aspects are tremendous – I have to deal with that every day. The genetics are also very interesting, and not just for type 1. Being Latino and with a heavily Latino patient population, I see this daily as well, and also the tremendous degree of heterogeneity there is between different people with the “same” disease – type 2 diabetes. Some appear to be much more insulin resistant than others, and while our tools are better, our ability to measure and understand those differences and the implications for their treatment are still quite primitive. The fact that science gives us a way to figure these things out and use that to make people’s lives better is why I love it.” 

What this says is that we touched on a disease that touches so many people in so many different ways, not just the individual with diabetes but also their family and friends.

But this all began with the Hangout and a look at the latest research, including Kevin and Howard’s discussion of their new device that could prove a powerful tool for people with type 1 diabetes. This project has funded in part by grants totaling over $30 million from CIRM.

If you missed the conversation the first time around you can catch it all by watching it on our web site. There’s a wealth of information there and it’s started a conversation that we are going to keep following in the months and years to come.

To learn more about CIRM-funded research related to diabetes, visit our fact sheet.

kevin mccormack

NFL Quarterback’s Super Bowl Bid Doesn’t Validate his Unproven Stem Cell Treatment

Peyton Manning (courtesy Jeffrey Beall/Wikimedia Commons/Flickr)

Here in San Francisco, 49ers fans are still stinging from their football team’s defeat up in Seattle last Sunday. But there’s no denying reality: the stage has been set for Super Bowl XLVIII between the Denver Broncos and the Seattle Seahawks.

One of the popular stories during the two-week lull before the big game is the impressive comeback of Broncos quarterback Peyton Manning. After two major neck injuries in the 2006 and 2010 seasons, Manning was thought to be all washed up. Instead he’s had a record-setting season.

Manning’s Super Bowl bid and comeback from injury have also prompted the revisiting of his decision to get an experimental stem cell treatment in Germany in September of 2011. On Tuesday, the title of an article carried by Voxxi.com asked, “Peyton Manning: Did stem cells save the quarterback’s career?

Your answer might be “yes” just watching Peyton’s return to elite status. But the details provided in the article show that there’s no solid evidence that his trip to Europe had any benefit to him or helped advance the stem cell field as a whole.

Manning’s treatment apparently involved the harvesting of stem cells from his own fat tissue (probably from his belly) that was injected into his neck. This procedure is not approved in the United States and it’s unclear whether the right type of cells is even present to have any beneficial effect. It’s likely that this fat tissue contained mesenchymal stem cells, an adult stem cell which can form bone, cartilage, fat, or muscle.

It’s potentially dangerous to inject uncharacterized stem cells that haven’t been matured into a specialized cell type. Recently a case of an untested cosmetic stem cell treatment grabbed the headlines in which the patient’s mesenchymal stem cells were injected around the eyes. Three months later pieces of bone formed in the patient’s eyelids causing excruciating pain.

All of this is to say that there’s a reason the Food and Drug Administration (FDA) requires a lengthy, rigorous process to begin and then run clinical trials for the approval of any stem cell-based treatment (or any drug for that matter): to provide evidence that the therapy is safe and effective in a large cohort of patients.

To people who are currently suffering from incurable diseases, these clinical trials can’t happen fast enough and can lead them to look upon Manning’s case with false hope. Larry Goldstein, a CIRM grantee and director of the UC San Diego Stem Cell Center, is quoted in the article and echoes this theme:

When a highly visible celebrity athlete chooses to undergo an untested/unproven therapy, and if they happen to get better without knowing whether the therapy is what caused the improvement, they encourage many other people to ignore scientific evidence and to substitute hope and blind trust for proof. The downside is that many people might be hurt by subjecting themselves to a risky procedure, or procedure with unknown risks, when there is no evidence of benefit to be gained.

Ultimately, Manning had a cervical spinal fusion surgery, which makes it even murkier what impact the stem cell therapy had on his spectacular season. So while I’ll be rooting for Peyton when he steps onto the field a week from Sunday, my hope is that people won’t follow in his footsteps to try unregulated and unproven stem cell therapies. As the article sums up quite firmly in its conclusion:

It is important for the public to understand there are legitimate reasons stem cell therapy is not yet approved for spinal injuries, and even though Peyton Manning has had a phenomenal career post-surgery and therapy, none of it can yet be attributed to the stem cell injections, regardless of what supporters of the treatment may indicate.

For more information about unregulated stem cell therapies abroad and in the U.S., visit our stem cell tourism page

Todd Dubnicoff

Surprising finding with cancer stem cells drives home the need for testing any hypothesis.

In science a logical hypothesis is not good enough. You have to do the science to put the logic to the test. A team at Ohio State proved this in spades in a recent study looking at cancer stem cells.

Specifically looking at oral cancers, the team compared those cancers associated with human papillomavirus (HPV) and those not associated with the virus. Since cancer stem cells are believed to be associated with tumor recurrence, and patients with HPV-positive tumors have better outcomes from treatment, the researchers hypothesized that HPV-positive tumors would have fewer cancer stem cells.

They found just the opposite. The HPV-positive tumors had anywhere from 2.4 to 62 times more cancer stem cells than the virus free tumors.

HealthCanal ran the university’s press release that had a quote from the senior researcher, Quintin Pan:

We show that high levels of cancer stem cells are not necessarily associated with a worse prognosis in head and neck cancer, a finding that could have far-reaching implications for patient care.

The team suggested that HPV-induced head and neck cancer may be highly curable because the cancer stem cells associated with it are different than with HPV-negative tumors and are more sensitive to therapy.

Sounds to me like they have set up another hypothesis that is ripe for testing.

CIRM funds a disease team that plans to begin a clinical trial in the next year or two using drugs to attack cancer stem cells in solid tumors.

Don Gibbons

Hangout with us tomorrow, it’s one hour that could change your life

Photo courtesy Fotos GOVBA

It’s been well known for many years that the number of people with diabetes is on the rise, but the sheer impact of that increase is staggering. According to the American Diabetes Association (ADA), the annual direct and indirect health care costs associated with diabetes rose to $245 billion in 2012. That’s billion with a ‘b’. And it’s an increase of 41 percent over just 5 years.

While the causes of the increase are many the solutions are far from easy, particularly for type 1 diabetes which is not caused by lifestyle factors but by the body’s inability to produce insulin.

On Thursday, January 23rd from noon till 1pm PT (3 – 4pm ET) we are holding a free Google Hangout to look at the progress being made in searching for stem cell treatments for diabetes.

We’ll have several experts and a Patient Advocate joining us online to talk about the latest and most promising research. Two of those experts are from ViaCyte, a San Diego-based company that has a Disease Team award from us and has developed a device they hope will be able to help people with type 1 diabetes. The device is about the size of a credit card and it is inserted under the skin where it can not only measure when blood sugar levels are low, but it can also secrete insulin to help restore those levels to normal.

We’re also going to be joined by Dr. Francisco Prieto, a practicing physician and researcher with an expertise in diabetes and a long-time active member of the ADA. Dr. Prieto also happens to be the Diabetes Patient Advocate member of our governing Board, the Independent Citizens Oversight Committee.

The fourth guest is Chris Stiehl, a longtime Patient Advocate who has lived with type 1 diabetes for more than 50 years and who can bring a lifetime of experience to the discussion, and his hopes for the future.

It promises to be a lively, engaging and informative hour. And it’s all free! And if you sign up on Google + (which is also free) you can post questions for the experts to answer.

To join us all you have to do is click here

We look forward to seeing you there.

kevin mccormack