Editors' ChoiceMuscle-Wasting Diseases

A Stem Cell Factory in the Making!

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Science Translational Medicine  28 Jul 2010:
Vol. 2, Issue 42, pp. 42ec118
DOI: 10.1126/scitranslmed.3001505

Stem cells have the potential to divide and thus self-renew indefinitely in the body, as well as to differentiate into specialized cells. However, their ability to self-renew is limited when they are grown in the laboratory, especially when they are cultured on plastic dishes, which creates a major hurdle in their development as a therapeutic tool. Culturing cells with a matrix or support and using appropriate media allows closer simulation of in vivo conditions. Now, Gilbert et al. demonstrate that growing muscle stem cells (MuSCs) on soft supports that imitate the elasticity of muscle improves the cells’ self-renewal and muscle repair capacity.

Using different percentages of the polymer polyethylene glycerol, the authors produced hydrogels with a range of rigidities, including one with an elasticity similar to that of mouse skeletal muscle. Laminin, an extracellular matrix protein with adhesive properties, was crosslinked to the hydrogel. MuSCs cultured on the most pliant hydrogels retained their “stemness” better, as seen by their improved survival and self-expansion and low expression of the differentiation marker Myogenin. The authors also tested the cells’ engraftment capability—their ability to produce muscle fibers in mice—which is a critical factor for assessing the stemness of MuSCs. The cells cultured on plastic had the worst engraftment capacity, whereas those cultured on the softest substrates showed a better extent and rate of engraftment. In an in vivo muscle injury model, the MuSCs cultured on the most pliant substrate homed to the site of injury and regenerated the injured tissue. These studies demonstrate that growth on soft substrates drastically improves the ability of MuSCs to regenerate while allowing them to retain their stemness. This result could be an important determinant for the development of cell-based therapy for muscle-wasting diseases and may have implications for culturing stem cells of other organs.

P. M. Gilbert et al., Substrate elasticity regulates skeletal muscle stem cell self-renewal in culture. Science Express, 15 July 2010 (10.1126/science.1191035). [Abstract]

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