Bad news for adult stem cells
One of the most promising types of adult stem cells, the MAPC or Multipotent Adult Progenitor Cell, originally discovered by Catherine Verfaillie's group and published in nature
, has fallen on hard times according to NewScientist
The results proved hard to repeat, and for more than six months from late 2003 even Verfaillie's own group was unable to isolate the cells. When New Scientist looked more closely, we found that six plots from the Nature paper and its supplementary information were duplicated in a second paper, published at about the same time in Experimental Hematology (vol 30, p 896), even though they were supposed to refer to different cells, taken from different mice. The plots described "marker" molecules on the surface of the cells, supposedly characteristic of MAPCs.
After New Scientist questioned the results, a panel of experts reviewed the data. Verfaillie, now at the Catholic University of Leuven (KUL) in Belgium, has since written to the two journals informing them of problems with data within the two papers, stating: "It was [the experts'] consensus opinion that the data were flawed and should not be relied upon as accurate representation of MAPC marker profiles."
The flaws she refers to do not relate to the duplications in the papers. These duplications, Verfaillie told New Scientist, were a simple mix-up. She stands by the claim that MAPCs can develop into most of the body’s tissues, and argues that later papers have described reliable methods for identifying them. In her most recent paper, Verfaillie and Irving Weissman, a stem cell biologist at Stanford University in California, showed that MAPCs can give rise to all the cell types found in blood, but it is still unclear whether MAPCs are as versatile as she claimed in the original Nature paper.
This is bad news. When these cells initially came out I remember we did try to get them. First we were told that the culture conditions were too difficult, then that there were intellectual property problems etc., excuses excuses. When we asked to come study it, they hemmed and hawed and said the cells really could only be successfully cultured in their lab and they were very finicky. Eventually we just gave up. However, the issue of repeating the results with MAPCs has become critical as her group continues to publish on them without other labs adopting the technology, and they simply should not be allowed to publish another paper on these cells until another lab can replicate at least some
of these results or use them for new applications.
Now we have word of data being duplicated by her group in more than one paper (a no-no in science) and that other labs have had the same experiences in terms of difficulty acquiring and growing the cell. I'm really thinking the usefulness of these cells is essentially unproven. Even the papers they've continued to publish such as this one from J Exp Med
on the hematopoietic potential of these cells are much less impressive than the initial results. In this case, they showed that MAPCs might supposedly be a hematopoietic stem cell progenitor (ha ha) because when you put thousands of them in a lethally-irradiated mouse, some of them were able to reconstitute their hematopoietic system. This claim is pretty specious considering thousands more MAPCs had to be used compared to HSC (of which under 10 cells can rescue the blood supply of a lethally-irradiated mouse).
Big trouble in adult stem cell land for sure. Now if I were Charles Krauthammer
or some other New Atlantis/First Things/right wing fundamentalist writer,
I'd suggest it's because the study of adult stem cells is so corrupting and foul that people who research them can't be trusted. However, not being a total idiot, I'd just point out that in all fields you occasionally encounter difficulties replicating results, the rare liar etc. We'll see how this pans out, I'd be really shocked if there were a fabrication here, but there's definitely some back-pedaling from this group and the whole "mix-up" excuse for data duplication? That's a poor excuse.
Labels: science, stem cells
Adult Stem Cell Tripe
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.
- 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
- Atala's research does not suggest these cells have equivalent plasticity as embryonic stem cells (although they are quite plastic).
- 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.
- 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.
- 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.
- They only showed absence of fusion in vitro not in vivo in recent studies.
- 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