A TGIF weekend reading list of new stem cell pubs & headlines

In case you have some free time for reading this week, here’s a list containing an assortment of interesting research articles and stem cell headlines. I’ve thrown some oddballs in there too including one article from May 1983, when I was just finishing up junior high. No, I didn’t write it. And no the headline for this current blog post is not referring to stem cell-themed pubs where you can go get some ale made from stem cells, but that’s not a bad idea, right?

Yeah, it’s been one of those long, busy weeks and it’s only Friday. And from the TGIF archives a piece from last year including stem cell soup, Kim Kardashian, and zombies.

And now the list.

PNAS, Butts, Et al. Figure 5H 2017

Newsy pieces

Research & other journal articles

And the one from 1983, Stem Cell is a Stem Cell is a Stem Cell. But is it? This reminds me of a fake journal name I came up with some time ago I imagine someone doing as a knockoff of the real top stem cell journal Cell Stem Cell. The fake journal name?

Stem Cell Stem Cell

My whole crazy list of fake and maybe future real stem cell journals with wacky names is here. Good for a laugh.

The backstory on my opinion piece in SF Chronicle critical of CIRM lobbying

Today an opinion piece that I wrote about CIRM was published in the San Francisco Chronicle. The unusual element here is that the article is critical of CIRM. More specifically I raised concerns about a recent political trend at CIRM under its new President Randy Mills lobbying for dramatically weaker stem cell regulatory oversight. The Chronicle piece was first posted online on Thursday on the paper’s website. I encourage you to read it when you get a chance.

CIRM 2.0

For a decade I have been one of the most consistent voices advocating for CIRM, its future, and all the great things that it does so it wasn’t an easy decision to publicly criticize the agency at this point. I’m still a big backer of CIRM, which made this even harder.

For me the tipping point to action was Mills’ recent opinion piece on Fox News with former Republican Senator Bill Frist that I believe was anti-FDA in tone and utilized hype (e.g. words like “miracles”, “gift”, and “beautiful” medicine) to promote a deregulatory agenda. This extreme plan includes conditional approval of unproven stem cell therapies and elimination of the requirement for Phase III clinical trials in certain cases, which would be very risky to patients and the stem cell field.

Mills also recently gave a speech at a conservative group (the self-styled “Bipartisan” Policy Center or BPC at which Frist is a leader) that counterproductively characterized the FDA as the one big problem for the field. Note that BPC also wants to charge patients to be in clinical trials to get experimental therapies. Historically if anything changed hands in such situations it was patients getting something in return for being so brave to be in clinical trials.

As I pointed out in my opinion piece in the Chronicle, the stem cell status quo is not getting the job done, but this is only in part due to the FDA and the changes that BPC and CIRM are advocating for are too radical. These proposed changes also fit with the REGROW Act, a bill that would codify many of them. REGROW would force the FDA to conditionally approve stem cell therapies that frankly are just not ready for primetime, putting patients at great risk. Note that the big changes being lobbied for in FDA regulations would only apply to adult stem cells. I favor more careful changes at the FDA such as using Breakthrough designation for stem cells, something the FDA has not yet done. They should.

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TGIF Science: funding, CRISPR v. NgAgo, secrets, Zika, & more

Some stuff on my mind for our TGIF Science this week.

Research Funding Ups: NIH. Is it my imagination or is NIH funding slightly improving? This is the overall vibe I’m hearing from the trenches.

TGIF science dart board

Modified Wikipedia image

Research Funding Ups and Downs: CIRM.  CIRM funded some basic research to the tune of a total of $4 million, which is great. On a personal level, just wish my “great idea” had fared better in review there. Kind of a downer, but after a while you get a really thick skin.

I’m still trying to decide what I think of CIRM 2.0’s grant review, especially their “positive” pre-review where there is no scoring or comments. You either make it or are triaged with no explanation or score given to applications. No sour grapes here from me on this particular DISC1 CIRM grant review, but even though my proposal made the cut to get fully reviewed, the actual review was too short, just a handful of vague sentences in total. That’s not helpful.

Secret genome meeting? I’m still scratching my head over that “secret” meeting on a synthetic human genome over at Harvard. They closed the door on the public, the press, etc. The reason given was that a journal had embargoed the heck out of ideas that would be presented at the meeting or something like that. 

CRISPR obsolete soon? George Church was quoted that CRISPR will be obsolete soon because of synthesizing entire genomes from scratch instead (see secret meeting entry above). Then of course there’s the upstart NgAgo that could be simpler and with broader applicability than CRISPR. What do you think of CRISPR versus NgAgo?

My sense is that talk of CRISPR obsolescence is premature kind of like Mark Twain’s quote that reports of his death were exaggerated.

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Top 10 stem cell stories of the year 2015

liver organoidWhat were the top 10 stem cell stories of the year?

What were the biggest news and science headlines in the stem cell field in 2015, whether good or bad?

Below are mine. What are your top 10 stem cell stories of the past year? Let us know in the comments.

  • Organoids explode. Stem cell-based mini-organs (organoids) have exploded in terms of impact in the last couple years. 2015 had many examples of these super cool human organs in a dish made from stem cells. Organoid technology has huge potential for teaching us about human organ development and function as well as disease pathogenesis and treatment. I recommend this interview by Alexey with organoid pioneer Madeline Lancaster for more on this exciting trend.
  • Clinical trials pile up. More good news. The number of real, promising stem cell clinical trials continues to build. This is fantastic and shows the continuing maturation of the stem cell/regeneration medicine/cell therapy fields. Think about where things were 5-10 years ago with stem cell clinical trials and you see how much progress has been made.
  • Sale of CDI and Ocata to Japanese pharma. Japan continues to show leadership in commercializing stem cells and regenerative medicine, and this in part manifested in 2015 with the big-time purchases of two American stem cell biotechs by Japanese pharma companies. Does the nation of a biotech company matter in this day and age? Are pharma acquisitions of small stem cell biotech good news or bad or some combo of the two? We can expect more corporate acquisitions in the stem cell arena in the coming year. Stay tuned for my top predictions for the stem cell field in 2016.
  • Stopping of IPS cell clinical study in Japan with broader regulatory switch there to allogeneic IPS cell focus. The pioneering macular degeneration clinical study using IPS cells in Japan was stopped this year and now a second IPS cell study (Parkinson’s Disease) there has been delayed. Regulatory changes now mandate that IPS cell clinical work be done with allogeneic cells. This change still remains somewhat of a mystery given the big potential of IPS cells on the patient-specific front using an autologous approach. We’ll hear a lot more about this in 2016. Another regulatory change in Japan is the move to allow charging of patients for clinical trial participation. I’m not a fan of this change to put it mildly.
  • CRISPR. Of course CRISPR is not specific to stem cells, but it opens new doors to understanding stem cell biology and development, particularly in the human research sphere. The genetic research on human stem cells that has opened up because of CRISPR is very exciting.
  • Human genetic modification on the table. Related to the above, gene editing of human pluripotent stem and germ cells has big ethical and social implications. The potential future production of genetically modified human beings via primordial germ cell or pluripotent stem cell editing raises big, thorny questions. Whether we are talking about genetic modification of somatic cells for therapy or production of actual designer babies, this topic was a hot one in 2015. For more, check out my new book, GMO Sapiens.
  • Stem cell clinics continued to bloom. From Internet searches to patient contact, the data out there are consistent with a continued rapid growth of stem cell clinics pitching at best unapproved stem cell interventions to at worst stem cell snake oil.
  • FDA action absent still on predatory clinics. For two years the FDA has practically speaking done nothing to address the exploding problem of stem cell clinics (see above) selling unapproved stem cell “treatments” to tens of thousands of patients in the US. We cannot forget about stem cell tourism, but the stem cell clinic problem in the US is massive and growing, and only made worse by an FDA that appears to either have mixed feelings on it or simply be moving in slow motion. Something’s got to give on this and I thought that would happen in 2015. Maybe it will in 2016.
  • Celebrities as advertising for stem cell clinics. Also in the dubious sphere we saw in 2015 an acceleration of celebs being the top drivers of patient traffic to stem cell clinics. Gordie Howe made the biggest news, but then there was Bart Starr and many others. For every famous person who puts themselves at risk or who is put at risk by their families looking for hope from stem cells, how many ordinary people follow suit and how many people will lose precious savings and potentially be hurt?
  • CIRM 2.0 picks up pace. Ending with some good news, the new incarnation of The California Institute for Regenerative Medicine (CIRM) as CIRM 2.0 (a name I admittedly enjoy saying as I coined the term) continued to build momentum in 2015. CIRM 2.0 has a distinctly clinical focus. The agency is picking up the pace on issuing RFAs and new funding. 

Stem Cells on the Mesa: Highlights from Heather Main

By Heather Main

Mesa, one of my first Spanish words since moving to California. The isolated flat-topped hill with steep sides where I have just had the pleasure of listening to some of the best basic and applied science. Mountains of various sorts formed the metaphor of CIRM 2.0 with Randy Mills (President/CEO of CIRM) describing the ‘giant boulder of love and happiness’ that academia pushes and industry pulls over the mountain of regulation, safety and efficacy bringing cures to patients. The streamlining of regulation makes the mountain smaller to decrease both the push and pull needed.

The meeting was a nice mix of academic and applied research, highly evident was the drive that CIRM funding has ignited in California. Of interest, after 5 years of 91% academic CIRM funding, the next 5 years is focusing towards critical funding towards industry translational projects…CIRM 2.0

Listening to Elaine Fuchs makes you question your worth in the field and when this woman will get a Nobel Prize for her contributions to stem cell sciences. The number of ‘Cell’ and ‘Nature’ references with her name on it in her talk demonstrate her unique ability to conquer the highest levels of science consistently throughout her career. A career spanning therapeutic skin stem cell application to stem cell niche determination, quiescent stem cell identification and now cancer stem cell quiescence, the lessons outlined by Elaine’s Keynote address form a foundation basis for stem cell sciences in both cellular therapy and cancer applications.

Other highlights for me included:Stephanie Cherqui, Ph.D

Stephanie Cherqui (at right), discussed the nanotubular highways for intercellular organelle transport with HSC cellular therapies that lead to macrophage differentiation and delivery of healthy lysosomes for Cystinosis disease rescue phenotypes.

Samuel Pfaff talked about his lab’s identification of miR218 as the most specific motor neuron marker known to date and the mechanistic possibility of its loss of activity, leading to an increase in gene expression deleterious to motor neuron survival, a possible mechanism for ALS.

Shyni Varghese (at left)Shyni Varhese, gave a great talk on production of bone from endogenously recruited cells using hydrogels engineered to bind minerals. The minerals were sufficient to produce bone in acellular scaffolds, while absence of mineral loading lead to fat formation. There was even novelty in Isaac Newton shaped bone deposit.

Pilar Ruiz-Lozano discussed amazing results using FSTL1 loaded collagen matrix to rescue heart regeneration following infarction, from mouse to pigs. The specific activity of FSTL1 from epicardium was essential to this regenerative function, in contrast to non-regenerative glycosylated FSTL1 produced in response to injury by the myocardium.

Joseph Metzger discussed stabilization of Duchenne Muscular Dystrophy dystrophic muscle membranes. These Poloxamer 188 ‘band-aids’ strengthen weaknesses in dystrophic membranes to avoid catastrophic Calcium entry that leads to cellular death. While super interesting, this is really a band-aid treatment, as Joseph says, just like Type 1 Diabetes, there is still room for gene and cellular therapy based cures.

The most confusing part of the meeting for me was the Thursday night ‘public forum’. I’m not sure what this means in California but the public forums I have attended have a majority of audience members from the public and attempt to pass knowledge and excitement about stem cells to a lay audience. While there was some fantastic science, I don’t think I would have understood a word in regard to ‘The promise of regenerative medicine: are we there yet?’ if I was a member of the public.

As my first time at Stem Cells on the MESA I was really impressed by the attitude I sensed, that solid science combined with effective clinical and commercial translation strategies are essential to successes in our field. That basic research is not enough. Second, it was nice to see an equal and unbiased appreciation for material sciences applications, gene therapy treatments, cellular therapy applications and endogenous repair applications. Whatever gets to the post first should ‘win’ for the sake of the patient.