Molecular signature, metabolic profile and therapeutic potential of human myogenic reserve cells

Dr. Thomas Laumonier, University of Geneva

Abstract

 

Satellite cells (SC) are Pax7+ tissue resident muscle stem cells, essential for muscle regeneration. SC are therefore considered as a potential stem cell source to treat skeletal muscle diseases. Nevertheless, as other primary muscle stem cells, SC are difficult to expand in vitro without dramatically reducing their regenerative potential. We have recently demonstrated that human myogenic reserve cells (RC) are quiescent myogenic stem cells with properties required for their use in cell therapy i.e. they survive, they form new myofibers and they generate new Pax7+ cells in vivo. Moreover, as compare to other muscle stem cells, RC hold the advantage to be generated in vitro in number compatible with possible therapeutic applications. 

In the current study, we propose to identify key molecular players implicated in the establishment and maintenance of human RC quiescence. Additionally, we will study metabolic and bioenergetic profile of human RC as metabolism is considered to be an active player in the regulation of cell state. Using low oxygen conditions in vitro, we will mimic in vivo conditions faced by stem cells after transplantation and evaluate their impact on human RC metabolism. Therapeutic potential of human RC in treating muscular dystrophy will be tested in immunodeficient mdx mouse model. Their capacity to improve the force-generation of dystrophic muscle will be evaluated. 

A better understanding of the molecular signature, metabolic profile and therapeutic potential of human myogenic RC should provide a solid foundation to determine if human RC constitute an appropriate source of muscle stem cells more directly pertinent to clinical applications.