What’s New in Pubmed – Stem Cells

I’m subscribed to some search feeds at Pubmed. Here’s what caught my eye this week in the Stem Cells feed. In this week’s post, I’ve got a good review of the recent Yamanaka paper everyone’s talking about.:

There were 11 new articles this week, one of which was open access.

I’ll start this off with the papers everyone’s talking about. There’s a great roundup of the press coverage at bioethics.net. Also watch Postgenomic and Technorati for blog coverage.

Here’s the link to the Cell paper by Takahashi et al. and the Science paper by Yu et al. (via) I won’t be discussing the Science paper, because my library has apparently let their online subscription lapse. Here’s the Science Magazine review.

The Takahashi paper was an interesting paper, and it went much along the lines of the earlier one which used mouse fibroblasts. The first problem they ran into was that the retroviruses that worked so well on the mouse cells didn’t infect the human cells with sufficient efficiency, and they needed very high efficiency for it to work because they only get one iPS for every 5000 transduced cells. To address this problem, they lentivirally transduced the cells with the mouse retroviral receptor Slc7a1, which boosted the transduction efficiency to 60%, before transducing with their Oct4, Sox2, Klf4, and c-Myc retroviruses.

This resulted in the generation of ES-like cells as shown by morphology, doubling time, gene expression analysis, chromatin state, and teratoma formation. Interestingly, the retroviruses were silenced in the iPS cells, so continued expression of the transgenes isn’t necessary for iPS maintenance. This is a good thing because c-Myc is a known and quite potent oncogene. In fact, 20% of the mice eventually developed tumors, at least partly due to reactivation of c-Myc.

Then, they differentiated the cells into cardiomyocytes and found expression of cardiomyocyte markers and the cells did that crazy spontaneous beating in the dish thing(WSJ has the video), but their PCRs showed evidence that there may be some undifferentiated iPS cells hanging around still.

They note in the discussion some of the problems with potential applications of iPS cells: The cells had 20+ insertion events each, meaning that the risk of dangerous insertional mutagenesis is way too high, and they further note that they don’t know what factors influence the efficiency of iPS cell generation. It could be that only when progenitor cells become transduced that iPS cells can arise, or the insertional mutagenesis could actually be an important part of the mechanism. There’s going to be some interesting research done to answer these questions. Obviously, a way to generate iPS cells that doesn’t involve viral transduction is key for even a hope of in vivo application. I’ve read about approaches that use site-directed insertion of genes, which could help things in this respect.

Finally, they close with this:

Human iPS cells, however, are not identical to hES cells: DNA microarray analyses detected differences between the two pluripotent stem cell lines. Further studies are essential to determine whether human iPS cells can replace hES in medical applications.

That’s as good as I could have put it myself, except I would have left off the “in medical applications” part. There has to be a medical application of ES cells first, before iPS cells can replace it.

Also interesting is a paper in JBMR by Holmes et al. wherein they show that Sca-1 null mice have deficient bone and reduced numbers of bone progenitors.
Holmes C, Khan TS, Owen C, Ciliberti N, Grynpas MD, Stanford WL. Longitudinal analysis of mesenchymal progenitors and bone quality in the stem cell antigen-1-null osteoporotic mouse. J Bone Miner Res. 2007 Sep;22(9):1373-86. PMID: 17547535 Related Articles

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