√ Update On Cirm’S Future: Will It Include 2020 Measure?

Robert Klein, 2017 CIRM Meeting. Image credit: California Stem Cell Report

The California Institute for Regenerative Medicine, more widely known as CIRM, has accomplished big things over the course of its history of about a decade and sparked a great deal of innovation, but what does the future hold for our stem cell agency?

CIRM has a new, respected President and CEO Maria Millan solving one of several challenges, but at present it doesn’t have an established concrete funding stream for when the Proposition 71 funding runs out in a few years. What happens next in terms of funding? Could a new bond measure a la Prop. 71 be initiated targeting the 2020 election cycle? There’s been a lot of talk about that idea, but what would its chances be of passing with voters here in California?

Over at California Stem Cell Report, David Jensen has been covering CIRM’s future funding options more often lately including a recent piece that discusses the 2020 proposition idea and a recent agency meeting to brainstorm future options. Jensen’s piece uses some evocative, discouraging words and strong adjectives to describe CIRM’s potential fate including “withering death.”

I don’t see things as so bleak and remain hopeful on the agency’s future. It’s unclear how California voters will be feeling about all this in 2020, but with our stem cell agency we are just now getting to the exciting part. The helping patients part. As a past grantee myself, I know how much the funding can make impact to advance science, whether basic, clinical, or somewhere in between.

At the recent brainstorming meeting on the agency’s future, there were apparently some upbeat reports of voter sentiment as described by Jensen:

“Robert Klein, a Palo Alto real estate investment banker who ran the 2004 campaign that created the agency, told the CIRM directors of a private poll that he said showed 70 percent of Californians supported stem cell research and continued funds for the stem cell agency.”

What do you think about our stem cell agency’s future?

In terms of clinically relevant science, it is at the most promising point in its history with support for loads of clinical trials. Not all of them will work out, but I’m convinced that some will and other fresh trials that could be initiated with CIRM’s new funding in the future beyond 2020 would bring more hope.

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√ List Of Regenerative Medicine Stem Cell Meetings For Rest Of 2018

This post contains a list of the remaining regenerative medicine and stem cell meetings for 2018. If you are interested in history, here’s our first ever meetings list for way back in 2012.

Here’s the 2018 list.

10th World Congress and Expo on Cell & Stem Cell Research, NY, NY USA, March 19-21, 2018.

iPSCs: A decade of progress and beyond. Keystone Meeting, Squaw Creek, California, USA, March 25-28, 2018.

April

Keystone Symposia: Organs and Tissues on Chips, Big Sky, Montana, April 8-12, 2018.

British society for developmental biology (BSDB) 70th anniversary annual spring meeting, Warwick U.K. April 15-18 2018.

Delivery of Stem Cell Therapeutics- the CIRM Alpha Stem Cell Clinic Symposium, Los Angeles, CA, April 19, 2018

May

ISCT 2018, Montreal, Canada, May 2-5, 2018.

June

Manufacturing and Testing of Pluripotent Stem Cells: IABS and CIRM, Los Angeles, CA, June 5-6, 2018

Hematopoietic Stem Cells: From the Embryo to the Aging Organism, Heidelberg, Germany, June 7-9, 2018.

Precision CRISPR Stem Cell Congress, Seattle, WA, June 12-14, 2018.

Stem Cells in Disease Modelling and Drug Discovery, Melbourne, Australia, June 17-18, 2018.

ISSCR 2018 Annual Meeting, Melbourne, Australia, June 20-23, 2018.

July

Notch Signaling in Development, Regeneration and Disease, GRC, Lewiston, MN, July 22-27, 2018.

Generating Diverse Cells and Networks in the Nervous System, Gordon Conference, Newport, RI, USA, July 29-August 3, 2018.

August

Using Cutting-Edge Technology to Dissect the Cross-Talk Between Stem Cells and Niche Across Different Organs, Gordon Conference, Waterville Valley, NH, USA, August 18-19.

Modeling Cell-Cell Interactions Governing Tissue Repair & Disease, Gordon Conference, Waterville Valley, NH, USA, August 19-24.

September

6th Cambridge International Stem Cell Symposium, Cambridge, UK, September 19-21, 2018.

From stem cells to human development, a conference from the journal Development, Surrey, UK, September 23-26, 2018.

October

Alliance for Regenerative Medicine: Cell & Gene Meeting on the Mesa, La Jolla, California, October 3-5, 2018.

CSHL Germ Cells, CSHL, NY, USA, October 9-13, 2018.

Regenerative Biology and Applications: Cell Differentiation, Tissue Organization and Biomedical Engineering (T3, Keystone, Pok Fu Lam, Hong Kong, October 15 – 19, 2017.

New York Stem Cell Foundation Research Institute’s 2018 Stem Cell Conference, Rockefeller University  New  York, NY, Oct. 23-24, 2018.

November

9th International Conference Tissue Engineering & Regenerative Medicine, Atlanta, GA, USA, Nov. 9-10, 2018.

Till and McCulloch Meeting, Westin Ottawa Hotel, Ontario, Canada, November 12-14, 2018.

December

Cell Symposia: Translation of Stem Cells to the Clinic, Challenges and Opportunities, Cedars-Sinai, Los Angeles, California, USA, December 2-4, 2018.

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√ Bigger Picture Study Casts Big Doubts On Stem Cells For Knee Arthritis Today

An x-ray of an arthritic knee

One of the most common claims made by unproven, for-profit stem cell clinics is that the stem cells they are selling can help knee arthritis and associated pain, but what is the evidence to back this up?

There are many problems with the claims of stem cells for arthritis being made across the U.S. In quite a few cases what is being sold isn’t even real stem cells. It often is an amniotic extract, which probably isn’t from actual stem cells anyway and is “dead.” But what about cases where real, live stem cells are being injected every day for knees arthritis and other kinds of joint problems?

The CIRM Blog recently covered the issue of stem cells for knee arthritis in large part inspired by a new comprehensive study that sheds major doubt on this approach. Some of the main take-homes from the study were nicely summarized by Kevin McCormack of CIRM:

“In a study presented at the Annual Meeting of the American Academy of Orthopaedic Surgeons, researchers contacted 317 clinics in the US that directly market stem cell therapies to consumers. They asked the clinics for information on the cost of the procedure and their success rate.

• Only 65 clinics responded


• Lowest price was $1,150


• Highest price was $12,000,


• Average price of $5,156.

Only 36 clinics responded with information about success rates.

• 10 claimed between 90 and 100 percent success


• 15 claimed 80 to 90 percent success


• 10 claimed 70 to 80 percent


• One said just 55 percent.

None offered any evidence based on a clinical trial that supported those claims, and there was no connection between how much they charged and how successful they claimed to be.”

Put it together and it paints a negative overall picture of the clinics in this sphere. Patients are paying around $5K for a kind of stem cell treatment where clinics are largely claiming 70-100% success, but yet have little or no evidence to back it up. The average cost data here fit well with the numbers in a poll I did about 6 months ago on this blog of what patients say they paid for stem cell therapies more generally.

McCormack has quotes both from the lead authors, Nicolas Piuzzi and George Muschler, of the study entitled, “The Stem-Cell Market for Treatment of Knee Osteoarthritis: A Patient Perspective“, which is published in Journal of Knee Surgery with some big picture perspectives and thoughts on the meaning of their work.

Basically, there’s a disconnect between the state of the clinical science in this area and what is being widely marketed for profit.  I’m not aware of massive patient side effects in this area so safety, while not assured by any means, is not perhaps the biggest issue. However, there is minimal evidence of efficacy from properly controlled studies. For instance, the authors of this study suggest potential benefit of bone marrow stem cells for knee arthritis, but although it did have a control group, it wasn’t blinded and was underpowered. Here’s a more recent, blinded study arguing for some moderate benefit, but it was underpowered as well and no benefit was seen after 12 months.

The bottom line in my view is that stem cells for arthritis from clinics directly marketing to consumers is most often going to be a big waste of money for patients. This is not to say that there’s no hope of stem cells for arthritis or specifically for knee arthritis, but caution is in order right now on this front. There needs to be more rigorous data on efficacy. I hope in the future we get that data as a field so we can have better clarity here. You can see some past posts including knee arthritis here and it’s apparent that for up to 8 years or more this issue has been percolating.

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√ Poll On Refunding Cirm On Eve Of Informational Legislative Hearing

Our California stem cell agency, CIRM, started as a baby even before I came to California in 2006 to start my lab here at UC Davis School of Medicine, but now CIRM or to use its full name the California Institute for Regenerative Medicine is I’d say a full-grown, mature 4dukt at about age 13 in humans years. Maybe CIRM years don’t go for the 7-year equivalent of dog years to human years, but perhaps 2 or 3 CIRM years to one human year.

I’ve covered the stem cell agency extensively here on The Niche over the last 8+ years. There have been critics and fans of the agency, and everything in between since its inception 13+ years ago, and many have weighed in here on this blog. While some critics used to focus years ago on the agency’s funding of embryonic stem cell research, the agency mostly funds other kinds of research now and its leadership has even been invited to speak at the Vatican the last couple years a few times. Other critics said the equivalent of, “Where’s the clinical trials?”, but with 49 funded clinical trials that issue could pivot now to be a positive that agency supporters can point to as a strength. Still other critics were focused more on economics of whether proposition funding in the billions was a wise investment.

Now that CIRM is in its prime but is poised to potentially run out of funds for new grants in the next year or two, how do you feel about it and would you support refunding it for another 10 years?

This kind of question might be on the mind’s of the California Legislature as it holds a hearing tomorrow on CIRM even though the hearing is not to my knowledge specifically focused on that question.

Take our poll below.

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√ Tgif Weekend Science Reads: Stem Cells, Prp, Cirm, Crispr, More

Sun, et al, PNAS 2018, part of Fig 1

What do you read on the weekend?

I wish for me it was at least in part some contemporary novel or science fiction, but that’s rare. More often than not it is almost all science. I do read the Sunday NY Times at least. I usually accumulate things during the week that I want to try to take a look at over the weekend (on top of the usual load of work like grant and paper reviews, writing of our own lab’s science, etc.) ranging from actual research articles to reviews to media pieces on science.

Here are some TGIF weekend reads for the weekend starting after midnight tonight, Friday August 17 unless you want to start early over a beer tonight.

Vision. “Stem cell treatment restores some vision in blind mice”. Many of us have hope for stem cells for various forms of vision loss in humans related to ongoing clinical trials. Much of the clinical trial work germinates from earlier model studies.

What’s CRISPR-SKIP? Check out this new paper that reports base editing mediated exon skipping: CRISPR-SKIP: programmable gene splicing with single base editors.

PRP. Here’s one that’ll make some stem cell clinics unhappy: Platelet-rich plasma does not promote stem cell-mediated cartilage repair. Clinics and even some university physicians are using PRP for all kinds of things including supposedly juicing up the power of stem cells to fix orthopedic injuries such as to joints. This new pub should spark some more sober reflection. PRP may have some healing potential, but it’s hyped too much and probably over-used.

State Medical Boards. “State Boards Turn Blind Eye to FDA-Sanctioned Docs.” An interesting investigative piece suggesting a troubling disconnect between the FDA and state medical boards. One section of this piece is on Thomas Gionis, a stem cell clinic doctor who a couple years ago got a warning letter from the FDA. He reportedly told the authors of this new piece by phone that “We’re not involved in that anymore.” before hanging up. There was some uncertainty if this physician or his previous clinics might still be doing stem cell stuff, but it looks like perhaps not so that’s notable. A recent FSMB report suggested that state medical boards might do more on stem cells. We’ll see.

Regeneration. “When it comes to regrowing tails, neural stem cells are the key.” How do some animals like lizards or salamanders such as axolotls regrow body parts like tails? Here we get more insights. Here’s the new PNAS paper itself. See a really cool part of Fig. 1 above from Sun, et al. comparing regenerated lizard and salamander tails with one notable difference being neural stem cell presence.

Micropatterning. “Bioengineers borrow from electronics industry to get stem cells to shape up”. I find the connection between electricity and stem cells more generally to be really interesting, even though that’s not what (as I thought originally from the title) that this linked to article is actually about. Micropatterning is pretty neat too and despite my skepticism, growing stem cells and other cells in confined, defined shapes (as has been reported by other groups) may some uses.

CIRM keeps pumping out funding for new, cool research even if such funding is now sometimes being pared back by the Board of the state stem cell agency. Here is a direct link to some of CIRM’s newest grants that are in the pre-active phase including one focus on trying to develop a new treatment for mutant histone H3.3 gliomas by the lab of Hideho Okada at UCSF.

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√ News Bites: Cirm, Anti-Mscs, Human Eggs From Stem Cells

Stem cells are always in the news so what’s up in the last week or two?

Human oogonia from stem cells stained pink; Saitou Lab

CIRM News

The dialogue over CIRM’s future is picking up a bit of steam. The San Francisco Chronicle did an in-depth piece on CIRM some weeks back and then opined that they didn’t feel supportive of another round of funding. I disagree. I think CIRM is a good future investment for California, but as a past CIRM grantee and stem cell advocate my opinion is probably not a surprise to readers.

Over at Science Translational Medicine, Derek Lowe expresses a pretty balanced view on the past and possible future of CIRM in a new blog post “Fighting It Out Over Stem Cells.”

MSCs = ???

It seems like MSCs are always in the news. Over at Nature, MSCs take a beating from Douglas Sipp, Pamela G. Robey and Leigh Turner. In their piece “Clear up this stem-cell mess”, they argue for abandoning the name MSC for stem cells altogether. They point out the explosion of pubs focused on MSCs (most commonly referring to “mesenchymal stem cells”) and also of clinics marketing MSCs. Another masalah is that MSCs can refer to a whole bunch of different kinds of cells and probably most often to mixtures of different cells. MSC has come to be an umbrella term and is sometimes misused, which is also very problematic.

It’s probably not realistic to think that the term MSC can be fully jettisoned, but I agree it’s a messy area. Of the two main ideas for what MSC could stand for besides as a name for kinds of stem cells, I think “mesenchymal stromal cells” is way better than “medicinal signaling cells” since the latter is way too aspirational. Neither term has caught on though.

The other broader issue is that these “MSC” cells are not really mesenchymal in the strictest definition of the word which means a specific class of embryonic/fetal tissues. I guess it was originally used since MSCs are often derived from tissues that came from mesenchyme.

Maybe a better term would something like mesoderm-derived stromal cells or mesenchyme-derived stromal cells? These aren’t very catchy though. It’d mean giving up the MSC acronym, but something like “stromal precursor cells” or SPC would arguably be the best.

Stem cell eggs (oogonia) in a different basket

A team led by Mitinori Saitou has published a report in Science on the production of human eggs (oocytes) from pluripotent stem cells. This is a huge deal. The science here is very interesting as they used a xenograft system (that’s why I wrote a “different basket”) for the eggs involving mouse ovarian stromal cells. However, there are even big societal implications as the authors point out as they end their abstract this way, “These findings establish the germline competence of hPSCs and provide a critical step toward human in vitro gametogenesis.” When I think about in vitro human gametogenesis, Hank Greely’s book The End of Sex comes to mind. I also covered some possible future issues related to stem cell-produced gametes in my books Stem Cells: An Insiders Guide and GMO Sapiens too. You can see an image of the human oocytes above at the top of the post from the Saitou Lab.

What do you think was the big stem cells news of the past 1-2 weeks?

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√ The Future Of California Stem Cell Research Cirm

The four words “California stem cell research” go nicely together and I hope they will continue to resonate in a special way to people around the world in the coming decade.

We are at a crossroads for stem cell research in California as the original form of the California Stem Cell Agency (CIRM) winds down. Will CIRM get a new infusion of billions in state funding via a ballot initiative a la Proposition 71 from more than a decade ago? Will CIRM instead find a different source, probably much smaller, of research funding such as via philanthropy? Could CIRM cease to exist within a few years?

CIRM has such strong clinical momentum right now, I hope it continues robustly for another 10 years.

Over at California Stem Cell Report, David Jensen has a piece on the possible new $5 billion California state ballot measure that may be in the works for next year to keep CIRM going. The article focuses a lot on Robert “Bob” Klein, who led the team that created CIRM originally. Jensen had a more than 1-hour interview with Klein, which includes some quotes that help clarify the ideas behind the potential next ballot initiative and future CIRM focus. For instance, there’s an interesting additional focus on patient access to new stem cell treatments down the road from Klein:

“The original initiative stated really a commitment to the idea of access….

“It’s my intention to actually put a directive in for funding the infrastructure to work on access, to work with insurance companies, to work with Covered California to work with Medicare, to make sure that there’s access, to make certain that public hospitals and public clinics in California get discounted prices.”

Klein also told Jensen about the need for emphasis on educating physicians about stem cells and regenerative medicine, a long-time focus of mine with my early publication that was a proposal for specific physician pelatihan in stem cells and regenerative medicine.

From Klein on this front:

“I’m looking at a directive section that deals with specifically broadening the doctors who are specifically educated. The only way you can do that is to buy a part of the residency time. Otherwise they don’t have time to do anything other than deal with current patients and current methodologies, which are radically insufficient as compared to the new cellular therapies.”

Klein’s potential emphasis on access is a smart one in terms of engaging voters and the pelatihan component including specifically of physicians also makes good sense.

Jensen’s piece indicates that insurance is a big part of the future stem cell treatment equation in California and more generally. In my view, a newly funded CIRM is also going to have to deal directly with the unproven stem cell clinic kasus in our state. With more than 100 such clinics here, Californians are at risk but so is stem cell research funding from these rogue efforts. The new bill on stem cell clinics could be the ticket, should it become law.

What about other sources of stem cell research funding here in California?

I’m thinking primarily here of what many of us refer to as “Roman’s Law“, which is The Spinal Cord Injury Research Program law (and now new bill) named after amazing stem cell advocate (and the first winner of The Niche’s Stem Cell Person of the Year Award) Roman Reed. It’s looking promising that Roman’s Law will get a new influx of state funding for stem cell research in spinal cord injury and paralysis. This would be great news.

I’ve also been brainstorming about whether there might be other entirely different future paths for funding of California stem cell research. While California has been very successful in getting NIH research funding for stem cell research by individual labs, the feds don’t fund state-wide efforts. The stem cell-related biotech industry in California is robust and should there be a few blockbuster successes from ongoing clinical trials here, which I expect will occur in the coming decade, this will likely draw in much more funding in that area.

If President Donald Trump takes action against embryonic stem cell research and there are more efforts against fetal tissue research, this could actually end up helping CIRM’s cause for additional funding. As many of us have noted, Trump could be an effective foil for the case for a future CIRM in a sense.

Overall, California’s stem cell future looks positive, but just how bright?

When I coined the phrase “CIRM 2.0”, I was already thinking about the post-Prop 71. future of CIRM. What will “CIRM 2020” bring? By the end of next year, we’ll have a much clearer sense of it. Jensen in a separate new post also directed readers to CIRM’s own newly-released brainstorming material for how to enhance itself for the future, which is a very interesting read here.

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