10 provocative stem cell questions: what are your answers?

heart stem cellsThere’s always debate about stem cells and regenerative medicine, right? There are very strong opinions in our field. Here is a list of 10 current, provocative questions. I have my own ideas about the answers to these. Weigh in with comments with your answers.

I’m going to do a follow up post with some discussion of the questions. I may do another follow up with the top 10 policy questions in our arena.

Here’s today’s list in no particular order. Continue reading

Top 10 reasons for optimism on Stem Cell Awareness Day 2016

Happy Stem Cell Day!

It is a tumultuous time for the stem cell and regenerative medicine fields, but despite this there are concrete reasons for optimism on this Stem Cell Awareness Day. I’ve listed my top 10 below. What else gives you a sense of optimism? You can also check out CIRM’s nifty stem cell awareness day page too, from which I borrowed the below image.stem-cell-awareness-day-2016

  1. More trials = road to progress. There are more real, robust clinical trials than ever and they are progressing past the early phases in some cases. The trials are piling up and while not all will succeed, some will. Keep an eye open for the for-profit, non-FDA-approved ones and steer people away from those.
  2. We are seeing a flow of clinical trial data too pointing to encouraging outcomes, but also to challenges to overcome (witness the preclinical study on IPSC for heart attacks that found efficacy but also arrhythmias). With that kind of awareness such hurdles can be overcome in many cases as the work progresses.
  3. The FDA held public meetings on stem cells. We can grouch about certain things about these meetings and we can ding the FDA for various issues, but it never before has engaged with the community like this on stem cells so it’s a good thing.
  4. Stem cells firing on all cylinders: adult and pluripotent. Adult stem cell trials are building, but so now are pluripotent ones. The best way to help the most people in the long run is with all the tools (types of cells) we can utilize. The notion of “adult versus embryonic”, for instance, as some sort of cosmic battle seems out of date. We need both and also IPSC as well as other types as yet to come.
  5. The stem cell clinic problem out in the open. Never before has there been this much information and awareness out there on the problem of stem cell clinics taking advantage of vulnerable people. For instance, see my recent article with Leigh Turner and the one from John Rasko’s group. I believe awareness will translate into action for the positive.
  6. Putting the fun back in funding? NIH funding trends are looking at least slightly better overall which will help with stem cell research. CIRM is continuing its life extension and will fund many more projects in years to come. Other states are funding stem cell research too. It’s still a bad time for funding but the trend lines are at least moving the right way.
  7. Much more educational outreach on stem cells. When I started blogging about stem cells in early 2010 it was very quiet out there on the Internet in terms of those of us trying to educate a wider community in a positive manner. That’s really changed now with quite a few blogs that at least touch on stem cells and a number entirely dedicated to stem cells and regenerative medicine. This is a positive change and it means the public has more resources than ever to learn about stem cells.
  8. IPSC clinically-relevant work is looking up. It was a decade ago that IPSC cells were “born” and there were great expectations. Now 10 years later there are tangible signs that these cells will have lasting, huge impact including both from disease modeling and more recently via potential future clinical use.
  9. Stem cells meet CRISPR and…boom! Okay so everyone is nuts about CRISPR no matter what kind of cells they study including me, but CRISPR-Cas9 gene editing combined with stem cells in particular equals great potential both for new insights such as into human development and also potentially clinically through designer stem cells.
  10. Stem cell biotechs & stocks hanging in there. It has always been tough going for stem cell biotechs and that is likely to continue quite a while longer, but many are hanging in there and could surprise you down the road. Others have been acquired by pharma companies or inked collaborative deals in the last year or so. In the long run some of these companies are going to change medicine.

Top 10 Google Stem Cell News Stories: Perspectives

What does Google think (if Google does indeed think) are top 10 stem cell news stories right now?

I took a screen shot below.

Here are some thoughts on those stories.

top-stem-cell-headlines

First, lung organoids are neat, but they have been grown before by several groups. Why is that the top story? I’d have to ask Google. Better PR? Still looks interesting and could have real impact for lung disease in the future.

The second story is on the transplantation of allogeneic IPS cells into monkeys without immunosuppression.This is an important finding with clinical impact from Dr. Takahashi’s group.

That third story seems odd to me. Seems like an over the top claim.

The fourth one with its “for the first time” I’m not so sure about and number five seems to be on the same story. I have doubts about that trial given the lack of detail and the potential for harm to patients. It sounds premature.

Then we have cancer stem cell stories at number six and another at number eight.

Number seven and ten both refer to the experience of one patient in the Asterias stem cells for spinal cord injury trial. Number ten’s headline is dubious from a scientific perspective with its “as a result” claiming the stem cells made the man better for sure. I really hope that’s true, but we don’t know yet although more recent data on more patients is encouraging. Controls are needed in the long run to iron things out.

Number nine is about stem cell clinics. It seems to be the only one mentioning the historic FDA stem cell meeting this week.

TGIF top 10 weird stem cell posts: magic testicle soup, Kim Kardashian, zombies, & more

kardashian-vampire-facialAfter six and a half years blogging here, I’ve seen so much crazy stuff. Not all of it was even “bloggable” due to its nature.

For TGIF, here are 10 of the weirdest posts from this blog over the years.

Where’s the Beef? Reality Check on Stem Cell Test Tube Burger Baloney

ZombieStem cells in my Pepsi? A new crazy stem cell myth

Please pass on bull testicles Soup No. 5 & on stem cell Soup No. 7

Haruko Obokata 小保方 晴子-like Game Character Conducts ‘Dangerous Research’

Stem cells sold for better sex part 2: bigger & better penis?

Strangest stem cell event of 2012: Moriguchi’s fake iPS cell transplants

Testimony in shocking supermodel stem cell fraud case: “I lied to patients”

Kim Kardashian vampire facelift: stem cells in there?Soup No.5

Beyond zombies: reviving dead people with stem cells & lasers?

Stranger than fiction: the electric stem cell bra for breast enlargement

Shinya Yamanaka at #ISSCR2016 on reprogramming of cells & scientists

The second day of ISSCR 2016 started off with a great session on pluripotency and plasticity, and the first talk was by Shinya Yamanaka. He changed the title of his talk to “Reprogramming of Cells and Scientist”. As with my other posts on this meeting, this one is a stream of quotes and impressions from the talk. The beginning was more autobiographical on his part and then the second half was on basic science. I really enjoyed this talk overall.

It’s now been a decade since Shinya Yamanaka’s seminal paper on mouse IPS cells. Shinya started his talk going back in time to the early 1990s of his postdoc at the Gladstone. He cloned NAT1 as a postdoc (Yamanaka et al. Genes & Dev, 1997).

Shinya Yamanaka

He found that NAT1 is required for early mouse development. He made NAT1 null mESCs and found that the NAT1 KO mESCs could not differentiate.

He got his own lab in 2000 and he and his group tried to induce pluripotency in somatic cells. It was 6 years later that they published the first IPS cell paper.

IPS cell technology has “reprogrammed me too” he said. One of the things I enjoy most about Shinya’s talks over the years (besides the wonderful science) is that he is very free with discussing what it means to be a scientist and how science effects scientists including on a personal level.

He noted that after human IPS cells, “I have been spending a lot of time in talking with people in government and industry and banks, and also spending a lot of time in fund raising.” I think this is what he meant by reprogramming of him by IPS cells.

“Some portion of myself is refractory to reprogramming. That part tells me I should enjoy basic research” and then he said that’s what my talk will be on: basic science.

He focused on NAT1 and its knockout in mESCs. Could NAT1 KO mESCs be in the ground state even without 2i treatment? NAT1-nulls even without 2i have the same morphology as WT cells in 2i. They did single cell RNA analysis. 2i makes WT mESCs more uniform in gene expression with higher Oct4 levels, etc. NAT1 nulls even without 2i are very similar to 2i WT cells. It seems NAT1 is an inhibitor of the ground state.

What about NAT1 in human ES cells?

Conventional gene targeting in human cells didn’t work. They could only get hets but no homozygous KOs (unpublished work of Kazu Takahashi). So it seems NAT1 is essential to human ES cells. Importantly, Kazu could get homozygous in the context of Dox NAT1 transgene. When you then remove Dox you get basically a complete NAT1 knockout. 2i LIF supports self-renewal of NAT1 null IPS cells. The NAT1 null IPS cell show higher than WT levels of OCT4 and NANOG as well as other pluripotency factors.

What does NAT1 do as a protein?

NAT1 is similar to eiF4G and it is known itself also as eiF4G2. They function in translational control. eiF4G is an essential linker in translational initiation. They searched for NAT1 binding proteins by doing flag tag IP. It binds to many translational proteins and many similar factors as eiF4G. There are a few things that eiF4G binds that NAT1 doesn’t.

Does NAT1 have general or specific translational regulatory functions? There might be some specific ones.

When NAT1 is turned off some specific proteins are elevated including KLF4 and PRDM14, two key TFs that are required for transition from primed to naive state. RNAs of these two are not changed so the change is at the translational level.

I can’t wait to hear more in the future about NAT1’s role in pluripotency.