Macrophages provide a transient muscle stem cell niche via NAMPT secretion

Promising Discovery In Satellite Cell Research

Details


Summary
Researchers discovered a protein which triggers satellite cells to proliferate and heal. In  sh with severe muscle damage, injection of NAMPT led to the regeneration of muscle and the return of normal movement. This study demonstrates that NAMPT, can be applied as new therapeutic for skeletal muscle injury and disease.


Methods / Design
Using muscle injury models in zebra sh, researchers systematically captured the interactions between satellite cells and the innate immune system after injury, in real time. By observing which cells migrated to a muscle injury in the  sh, the scientists identi ed 8 genetically different macrophages had a role in triggering the muscle stem cells to regenerate.
Further investigation revealed that a speci c subset of macrophages ‘dwell’ within the injury, establishing stem cell proliferation. Single-cell pro ling identi ed proliferative signals were secreted by dwelling macrophages, which include the cytokine nicotinamide phosphoribosyltransferase (NAMPT).

Researchers then removed these macrophages from the zebra sh and addwd the NAMPT to the aquarium water. Results showed that this  stimulated the muscle stem cells to grow and heal, effectively replacing the need for the macrophages.


Comments
These results differ from the 2017  ndings of Du, in which they identify macrophage released ADAMTS1 as promoting muscle stem cell activation [1].


While the observations of Du’s experiment are sound, I believe the recent discovery of NAMPT is more promising for the future of muscle stem cell therapy. The previous experiment was conducted under the thought that only two types of macrophages exist in the body, however the recent experiment revealed eight types of macrophages. This more in depth analysis of macrophage lead me to believe the results are more promising. If successful, NAMPT could lead to new therapeutic for skeletal muscle injury and disease which could help millions every year.


[1] Du, H., Shih, CH., Wosczyna, M.N.  et al.  Macrophage-released ADAMTS1 promotes muscle stem cell activation. Nat Commun 8, 669 (2017). https://doi.org/10.1038/s41467-017-00522-7



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