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A lesson learned from a regeneration study

We have briefly touched the subject of stem cell research in the last journal club. The challenge of developing “stem cell” as a useful therapy is three fold:

  1. Turning the clock of a differentiated cell back to the very beginning.
  2. Guiding the resulting dedifferentiated “stem cells” or any kinds of “stem cells” to develop into the appropriate cell types.
  3. Incorporating these new cells into the existing organ system properly.

In one sense, the premise of 1 and 2 is that 3 would happen automatically once you can get the Stem cells. They are not only expected to become the desired cell type, but also are expected to know what to do inside the body. This can be a tall order.

There is actually a lot to learn from basic research to see how mother nature deals with the regeneration problem. Salamander is a great regeneration model. If you cut its limb off, the cells in the wound region will grow back a limb to its entirety.

It has long been thought that these cells that are responsible for the regeneration process are pluripotent, or “stem cell”-like. A very interesting research has proven it is otherwise. The original cells in the limb actually remember their identities, and they will only grow back to their own kind. In other words, muscle cells will become muscle cells, and skin cells will become skin cells.


It looks like that instead of having some very specialized stem cells that switch all the way  back to the beginning, the differentiated cells just go back a few (?) steps and maintain their identities during the process. One wonders how this process is regulated at the network level and what has been lost in us that we do not have this capability anymore. Maybe this talent is still hibernating somewhere in our genome, waiting for us to turn it back on.


Sánchez Alvarado A. A cellular view of regeneration. Nature. 2009 Jul 2;460(7251):39-40. [PubMed][Nature]

Kragl M, Knapp D, Nacu E, Khattak S, Maden M, Epperlein HH, Tanaka EM. Cells keep a memory of their tissue origin during axolotl limb regeneration. Nature. 2009 Jul 2;460(7251):60-5. [PubMed][Nature]