Regenerative capacity of hypothermic treatment in induced human satellite cells
Satellite cells, characterized by the transcription factor Pax7, are the proper stem cells of the adult skeletal muscle. They have an enormous capacity for self-renewal and superb potential for muscle regeneration. It has only recently been recognized that muscle regeneration cannot occur when satellite cells are absent. However, satellite cells are notoriously difficult to study due to their low abundance and their dispersed location in the specific stem-cell niche, the space between basal lamina and sarcolemma of skeletal muscle. Once outside their niche, satellite cells differentiate into myoblasts and loose their stem cell properties. Therefore, expansion of human satellite cells for therapeutic purposes has not been successful so far. Recently, we have shown that human Pax7+ satellite cells can be expanded in vitro if cultured within their natural stem cell niche (Marg et al., J Clin Inv 2014). Furthermore, they can be transplanted into muscle of immunosuppressed mice and form multinucleated human muscle fibers. This procedure could still be markedly improved when HMFF were preconditioned by hypothermic treatment. Despite their desirable properties primary satellite cells will hardly become available in very high numbers necessary to repopulate large limb muscles for therapeutic purposes. We therefore aim to compare the regenerative capacity of primary human satellite cells to myocytes derived from human induced pluripotent stem cells subsequent to the same preconditioning procedure.