The WaPo, BBC, SfGate, CNN and many others are reporting on a ostensibly new type of stem cells derived from amniotic fluid (Nature Biotech link). While these come from amniotic fluid, they are not embryonic stem cells, since it's not clear that they are totipotent (can make all tissues), but the articles are suggesting that they might be.

Now, reading these articles and the Nature Biotech paper, I immediately had a bunch of red flags pop up in my head. Here's some of the problems that come immediately to mind.

1. Nothing about these cells suggests they are any more or less novel than cord blood stem cells and many other "adult" stem cells types which can be transdifferentiated in vitro
   
2. Atala's research does not suggest these cells have equivalent plasticity as embryonic stem cells (although they are quite plastic).
   
3. Conflicts of interest exist that cause concern about the timing of this release - the potential for ES cell debate in Congress this week, Atala being on the board of the company that uses these cells etc.
   
4. The method of purification of these cells (here's probably the most detailed article on them) is selection for c-kit, a common marker identifying adult stem cells - makes me think that these aren't any more exceptional than hematopoietic stem cells which can do many of the same tricks in culture but are of questionable in vivo untility for transdifferentiation.
   
5. No functional in vivo data exists on the totipotency of these cells - namely the isolation of equivalent cells from rodents and formation of chimeras to show pluripotency. This is really too bad since the authors do say they isolated cells from mice and rats, a chimeric injection experiment really would have been definitive and as a reviewer I would have asked for it before publication.
   
6. They only showed absence of fusion in vitro not in vivo in recent studies.
   
7. No evidence exists these cells are totipotent so claims they can replace embryonic stem cells are just as inappropriate with these cells as every other adult stem cell line that has had promise and ultimately failed to perform.

If you want to see what testing for pluripotency looks like with adult stem cells check out this old post on the spermatagonial stem cells, which seemed to have real promise. Critically, the formation of mice using the stem cells which would be proof of real totipotency - contribution in vivo to all three germ layers. The experiment would be useful even if the cells aren't totipotent because they can compare the relative potency to ES cells, and determine which tissues, if any, these cells will not contribute to. Until then, with the literature not showing the necessary experiments to justify these claims of equivalence to embryonic stem cells, I find it irresponsible for the researchers or the press to suggest some incredible breakthrough - especially in this political climate. This is really too bad, because Dr. Atala is an excellent scientist with a really impressive body of research in tissue engineering, and I hope this isn't a purposeful effort to reinject yet another unproven adult stem cell line into the debate over stem cells. I wonder if that was even his intention; it is quite possible his research being highlighted at a particularly sensitive time to help drive a political wedge. This publication is certainly interesting, but I worry it's being over-hyped in preparation for our coming debates on this science.

Labels: embryonic stem cells, stem cells