Grading my top 20 stem cell predictions for 2016: how’d I do?

Below are the 2016 stem cell predictions I made last year and their status now color-coded near year’s end. Green is right, orange is mixed bag, and red is flat out wrong.

Overall, I did better than most past years with only having entirely blown it on four.

Stay tuned later this week for my 2017 predictions, which looks to be a dramatic year in the field of stem cells and regenerative medicine.

The Score Card on 2016 Predictionsstem-cell-predictions

  1. Another stem cell biotech acquisition by pharma (recall Ocata (now finally sold to Astellas) & CDI in 2015). Grade: Some acquisitions, but not huge news.
  2. Charging patients for clinical trial participation, particularly in Japan due to the new policy and here in the US related to predatory clinics remains a hot topic. Grade:  Correct.
  3. Stem cell clinics and doping in sports flares up more. Grade:  not really the two together.
  4. Organoids continue to excite. Grade:  Correct.
  5. Bioheart and some other small stem cell companies struggle. Grade:  Correct.
  6. Stem cell stocks overall have a bad year. Grade:  Unfortunately, generally correct.
  7. Stem cell clinics ever more aggressively use celeb clients for PR and marketing. Why? It is powerful, effective, and essentially free advertising. Grade:  Correct.
  8. More news on human-animal chimeras. Grade:  Correct.
  9. FDA continues its slow-go approach to action on stem cell clinics/unapproved stem cell products. Grade:  Sadly correct.
  10. Pressure from industry and some academics on FDA to not regulate adipose products as drugs and/or to not enforce some other draft guidances including at the public hearing on the draft guidances. Grade:  Correct.
  11. FDA receives increasing public criticism for “slowness” on approving new stem cell therapies including from beyond the stem cell clinic industry. Grade:  Correct.
  12. One or more lawsuits against a stem cell clinic. Grade:  Correct in a big way. E.g. versus U.S. Stem Cell, Lung Institute, and Stemgenex.
  13. A new stem cell scandal pops up related to publication issues. Grade:  Correct. You just have to go visit Retraction Watch (e.g. the Spain mess), For Better Science, or PubPeer, and then also see the continuing Macchiarini debacle in particular.
  14. Some hiccups on mitochondrial transfer/3-person IVF in the UK or China. Grade:  Correct. Diseased mitochondrial carry-over and mito-nuclear cross-talk issues have popped up and deserve serious attention. Remarkably, nevertheless UK folks are going forward with it in humans anyway.
  15. The trend last year of increasingly blurred lines between legit research entities such as universities and dubious stem cell enterprises continues. This is worrisome. Grade:  Correct. For instance, see Rasko paper.
  16. Stem cell-derived human germ cells stay in the headlines. This has exciting potential for providing new windows into human development and tackling infertility, but also raises thorny issues such as human genetic modification. Grade:  Correct.
  17. ViaCyte has some big news. Grade: Not yet… 
  18. High-profile developments on veterinary use of stem cells. Grade:  Correct. 
  19. Animal cloning, particularly in China, continues to proliferate. Grade:  Correct.
  20. More rumblings on possible human reproductive cloning attempts. Grade:  Some here and there, but not much. See this piece on cloning focusing on 20th Anniversary of Dolly.

Blogging today’s FDA stem cell meeting: Part 2 Clinics, Policy & Ethics

The FDA is holding its first 2016 stem cell meeting today and you can read about some impressions of the morning session of this meeting here.

In this post, I’m focusing on the afternoon session, which has been mostly on policy and ethics, including on stem cell clinics.jonathan-kimmelman-fda

Jonathan Kimmelman from McGill University got the afternoon going with his excellent talk “Ethics, Evidence, and Regulatory Approval for Cell-Based Interventions“. Jonathan started his talk addressing the stem cell clinic situation in the U.S. and asking more broadly how regulatory authorities should establishment a benchmark for making experimental interventions such as stem cells available to patients.

He asked if there is a zero sum game between innovation and oversight? He argues there isn’t. They can actually work together. With oversight you maximize the amount of data per patient put at risk.

He used gene therapy taking decades (and still no approved therapy) as an example of the timeline for experimental stem cell therapies.

What about the idea of patients vs. bureaucracy? Is that a genuine dynamic? Are the most vocal patients democratic representatives of patients more generally?

jonathan-kimmelman-stem-cell-clinical-translation-talk

jonathan-kimmelman-stem-cell-clinical-translation-talk slide

In talking about the idea of safety vs. efficacy, he discussed risks of cell therapies.

He asked, “How do we as a society want to distribute the costs and burdens of medical uncertainties?”

How does this all tie in with the new 2016 ISSCR guidelines on stem cell clinical translation?

Key issues include the primacy of patient welfare and social justice. There should not be exposure of patients to unproven therapies outside of true clinical trials or in other unique circumstances (I’m thinking expanded access).

Jonathan also talked about concerns with pay-to-participate trials for stem cells.

Above is a summary slide from Jonathan’s talk.

stamina-stem-cell-protocol-problems

stamina-stem-cell-protocol-problems

Massimo Dominici, MD next gave his talk “Dissecting Unproven Cellular Therapies: The International Society for Cellular Therapy (ISCT) Position.”

Dr. Dominici talked about global stem cell clinic locations, the costs, and the global challenge here. He showed data from the important John Rasko Cell Stem Cell paper on global stem cell clinics. He also cited the example of the Stamina problem in Italy and the “weird” protocols involved there in that treatment. One patient died. See his slide above on Stamina, where UCT means unproven cell therapy. To sum up he indicated that a problem is confusion between unethical versus innovative cell-based approaches.

Peter Rubin, MD wrapped up the session on  “Clinical Adipose-Based Therapies.” Dr. Rubin is a plastic surgeon who studies adipose (fat) stem cells. He talked about autologous fat transfer versus adipose stem cell treatment. As to the former, he discussed the strong safety profile and good results with fat transfer outcomes (for instance with facial deformities from wartime injuries). There’s about 63% retention of volume induced with fat transfer in their experience. He reported that the # of cells in the fat tissue correlates with better outcomes. Tissue remodeling (not just volume) occurs. He did also mention how fat stem cells might be able to promote cancer recurrence or progression.

What about adipose stem cell treatments? Rubin called the basis for this as being “bioactive” cells from fat or the stromal vascular fraction, which someone from Wisconsin he says apparently calls colloquially “sushi”. I’m not sure I get that. Rubin uses an automated machine to make SVF. Lots of heterogeneity in SVF cell types. He talked about IFATs (a federation for fat tissue/cells). These cells make growth factors. They are using these cells in pre-clinical studies now (e.g. in rodents). Their clinical strategy under an IDE is to mix the SVF with the fat graft for traumatic amputation. He advocated for taking a responsible, evidence-based approach.

Overall, I found these talks to be really fascinating together linking together real-world experiences with stem cells in clinical use (responsible or not or even in the middle gray zone in some cases depending on one’s perspective) along with ethical and policy considerations as well as guidelines.

Important Rasko team paper on global distribution of stem cell clinics

Last week a team led by John Rasko of the University of Sydney published a very important stem cell clinic study also in Cell Stem Cell. Thus, there have now been two new reports on the state of the stem cell clinic industry both here in the U.S. and more globally.

Leigh Turner and I published our paper at the end of June on the American clinic industry, finding 351 businesses and 570 clinics selling non-FDA approved stem cell therapies. Rasko and colleagues did a much more global analysis including international businesses and their search approaches were different. This is a really fascinating, key new stem cell paper. I highly recommend it.

stem cell clinics map Rasko

Berger, et al. Figure 1c

 

They collected data on clinics all around the world, finding that this is a global phenomenon. The top ten countries by absolute number of clinics were the following: “USA (187 clinics), India (35), Mexico (28), China (23), Australia (19), UK (16), Thailand (14), Malaysia (12), Germany (11), and Indonesia (7)”.

Their team found somewhat fewer clinics than we did in the U.S., but their data also paint a picture of a large American industry marketing non-FDA approved stem cell interventions (see their map, Figure 1c, above).

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