Editors' ChoiceTissue Engineering

Stem cells flex their muscle regenerative potential

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Science Translational Medicine  08 Jun 2016:
Vol. 8, Issue 342, pp. 342ec93
DOI: 10.1126/scitranslmed.aag1872

Every bodybuilder can tell you that “feeling the burn” is a good thing, as minor muscular trauma leads to the development of new muscle fibers and increased tissue mass. Unfortunately, when the injury exceeds a certain threshold, muscles possess very poor regenerative capacity, leading to fibrotic scarring and fatty degeneration, which weakens tissue structure and function. Many biomedical engineers have focused on delivering mesenchymal stem cells (MSCs) and/or muscle satellite cells directly into the damaged site to develop into new muscle tissue, but these strategies have had limited long-term success. Pumberger et al. now provide evidence that MSCs can be delivered adjacent to the injury site and produce regenerative cues that act in a paracrine fashion to facilitate endogenous muscle repair nearby.

Prior attempts to engineer muscle regeneration in vivo have been suboptimal because exogenous cells possess poor engraftment and retention rates, and physiologically relevant growth factor delivery that mimics the biological milieu is difficult to achieve. This research team took a different approach where they used MSCs as biological “factories” to produce a variety of bioactive cues that would facilitate muscle regeneration. Culture supernatants from MSCs exposed to two stimulatory growth factor proteins, IGF-1 and VEGF165, enhanced skeletal myoblast behavior compared with supernatants from MSCs alone or media directly supplemented with IGF-1 and VEGF165, suggesting that these growth factors encouraged the MSCs to release muscle-regenerative molecules. To facilitate long-term MSC bioactivity in vivo, the MSCs were seeded onto protein-loaded alginate cryogels that slowly released the MSC-stimulating growth factors. When these constructs were implanted in rats near an acute muscle injury, the MSCs remained local and bioactive for weeks, inducing significant muscular regeneration, including enhancements in muscle density, fiber count, and vessel formation, as well as proper tissue remodeling and limited scar formation compared with damaged muscles exposed to scaffolds alone, scaffolds with only growth factors, or scaffolds with only MSCs.

Although more studies need to be conducted with chronic or long-term injury models and higher-order animals, this study puts forth exciting data demonstrating the potential for stem cells to act from a distance to repair skeletal muscle—an approach that can perhaps be leveraged to regenerate a wide variety of other tissues, especially those difficult to reach or are inoperable.

M. Pumberger et al., Synthetic niche to modulate regenerative potential of MSCs and enhance skeletal muscle regeneration. Biomaterials 99, 95–108 (2016). [Abstract]

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