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Ex-vivo Expansion of Muscle-Regenerative Cells for the Treatment of Muscle Disorders

Schaaf G, Sage F, Stok M, Brusse E, Pijnappel WWM, Reuser A and vd Ploeg AT

Skeletal muscle has an impressive regenerative potential. The cells that mediate muscle repair have unique properties that are not restricted solely to the formation of new muscle, but also contribute to the repair of damaged residual tissue. Recent studies have shown that freshly isolated muscle-regenerative cells maintain these properties, and contribute to muscle repair after transplantation to host muscle tissue. Muscle-regenerative cells are typically present in low numbers, and the yield of therapeutic cells from biopsies is low. Ex-vivo expansion of the candidate cells is therefore required. However, when cultured in vitro, the muscle-regenerative cells, and particularly muscle satellite cells, lose their regenerative capacities. This poses a major limitation on the introduction of cell-based therapies for muscle disorders. Here, we take the opportunity to review the promise of cell-based therapies specifically for the treatment of degenerative muscle diseases. We focus particularly on optimizing the conditions for expanding the cells in vitro in a way that maintains their regenerative properties.