Resurrection (non-zombie related)

As a fan of the Walking Dead television series, I was tickled to learn of an article¹ in this week's Nature Communications that reported viable muscle stem cells have been isolated from refrigerated cadavers 17 days after death! (And brought me thoughts of zombies.) The cells were even capable of regenerating new muscle cells in a dish. Not only that, the 17-day window was only a limit imposed by the lack of older human specimens and suggested the stem cells may survive beyond 17 days. The explanation for these observations was found in muscle stem cells recovered from mice that were dead for 14 days (refrigerated, of course). These mouse cells were found to be dormant, which may explain why they were able to survive for 2 weeks in the low-oxygen, starving conditions that are typical of dead tissues.

One may certainly ask if harvesting stem cells from the dead may be an option for future regenerative therapy. It seems very much like organ donation, at least to me. Alexey Bersenev has delved into this topic from a historical perspective and also discussed the possible applications in a very thoughtful post. I won't belabor his points here, but I highly recommend his work.

The one thing that stuck out to me in that article is the age of the donors—almost half of them were over 90 years old. And yet, it was still possible for them to retain a pool of stem cells in their aged muscles. I wondered if the skeletal stem cells from these donors may have morphed after acquiring genetic mutations over all those decades, or if dormancy insulated them from external stresses so that they can now be safely reanimated? If our muscles squirrel away stem cells over a lifetime, are those cell stocks refreshed periodically? If so, then it implies the stocks may harbor genetic damage that can have consequences for a transplant recipient, or maybe the cells just won't regenerate very well. On the other hand, if the stem cells are stored in a specialized, protective niche, then they may be fresh as daisies once they are revived.

I've been reading a few papers^2–4 that specifically discussed the effects aging has on muscle stem cells and their niche. The consensus is that even if this specialized niche does indeed insulate stem cells from most stresses, the niche itself is subject to all manner of intercellular signaling that can influence how well it protects the cells. As we age, that specialized niche and the stem cells within it are bathed in the same biomolecular soup that tells the rest of our body we're getting older.

All of this suggests to me that we will have to figure out the biological mechanism of aging if we want high-quality cells from older (and perhaps dead) donors. So for all the youngsters out there, wear your seat belt and don't drink and drive...otherwise, carry your donor card and save someone else's life.

Photo credit: zombie-warning by This is Awkward via Flickr (http://www.flickr.com/photos/reana/3238910501/)

References:

1. Latil M et al. Skeletal muscle stem cells adopt a dormant cell state post mortem and retain regenerative capacity. Nat Commun (Jun 12, 2012). doi: 10.1038/ncomms1890
2. Jang YC et al. Skeletal muscle stem cells: effects of aging and metabolism on muscle regenerative function. Cold Spring Harb Symp Quant Biol 76,101-11 (2011).
3. Carlson ME et al. Molecular aging and rejuvenation of human muscle stem cells. EMBO Mol Med 1(8-9),381-91 (2009).
4. Gopinath SD and Rando TA. Stem cell review series: aging of the skeletal muscle stem cell niche. Aging Cell 7(4), 590-8. (2008).