Editors' ChoiceRegenerative Medicine

Calling All Satellite Cells!

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Science Translational Medicine  14 Nov 2012:
Vol. 4, Issue 160, pp. 160ec206
DOI: 10.1126/scitranslmed.3005301

We might envy the physical power of Superman or the Hulk, but everyone’s muscles have their own superheroes—called satellite cellswaiting in the wings to answer the call for help after muscle injury. These powerful progenitor cells give muscle its remarkable regenerative capacity. Unfortunately, in cases of severe muscle injury or genetic muscular disorders, the native regenerative capacity of the body is not robust enough to come to the rescue. This gap has spurred scientists to pursue ways to boost muscle regeneration by using implanted satellite cells, embryonic stem cells, and other cell-based therapies. A major limitation of these therapies is the reduced capacity of transplanted satellite cells to survive, migrate, and proliferate after implantation. Now, Hong et al. describe a molecular pathway that controls satellite cell expansion in vivo and may provide a means to enhance therapeutic muscle regeneration.

Hong and colleagues examined the molecule hexamethylene bisacetamide inducible 1 (HEXIM1), which acts as an inhibitor of gene expression pathways required for muscle regeneration after injury. The authors created a mouse model that expresses one-half of normal amounts of HEXIM1 and then injected an injury-producing toxic compound into the muscles of the leg. Fifty days later, the HEXIM1-deficient mice displayed ~50% greater muscle mass in and a 21% increase in contraction force of the injured limb compared with the contralateral control limb. When the muscles were examined histologically, the authors found a twofold increase in the number of satellite cells in the HEXIM1-deficient mice. To test the therapeutic potential of these findings, the researchers isolated satellite cells from the HEXIM1-deficient mice and transplanted them into wild-type mice with muscle injury. The HEXIM1-deficient donor satellite cells displayed increased proliferation and expansion relative to transplanted wild-type cells.

The work of Hong et al. identifies a pathway that can be targeted to enhance therapies that have shown promise in humans. By treating isolated satellite cells with HEXIM1 inhibitors, it might be possible to greatly improve the cells’ regenerative capacity when transplanted back into injured muscle. In addition, HEXIM1 may provide a new therapeutic target for degenerative muscular dystrophies. Although the new work provides insights into mechanisms of muscle regeneration, further preclinical studies are needed to evaluate HEXIM1 inhibition as a potential therapeutic target in humans.

P. Hong et al., HEXIM1 controls satellite cell expansion after injury to regulate skeletal muscle regeneration. J. Clin. Invest., published online 1 November 2012 (10.1172/JCI62818). [Full Text]

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