The researchers wondered whether these "alert" stem cells could repair subsequent tissue damage more quickly than resting stem cells. They found that mice with one leg first experienced an alarm injury were able to repair muscle damage more quickly and effectively than after three days. Especially in the 24 day recovery period, the damaged muscle fibers of the mice subjected to the alarm injury were larger at each time point than the damaged muscle fibers of the control mice.
Surprisingly, muscle stem cells are also very alert to bone or minor skin damage. Conversely, other non-muscle adult stem cells, including bone marrow hematopoietic stem cells and muscle mesenchymal stem cells, are also alert to muscle damage.
Although it is not entirely clear how the body stem cells accept these warning signals, the researchers have discovered some key signaling pathways, one of which is controlled by the mTORC1 protein. This mTORC1 signal activates the production of proteins required for cell division and is known to play an important role in stem cell proliferation.
Another protein, HGF, is present in a latent form in the space between muscle stem cells and other tissue cells, which makes it well responsive to systemic circulation signals. When HGF is activated, it binds to the surface of stem cells and activates the mTORC1 signaling pathway. Rando and his colleagues found that blocking HGF-binding cells can prevent these cells from becoming alert in response to distant damage, but it is unclear what activates HGF.
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