Generation of skeletal muscle cells from embryonic and induced pluripotent stem cells as an in vitro model and for therapy of muscular dystrophies

Abstract

Introduction • Transdifferentiation of somatic cells in skeletal myoblasts • Myogenic cell induction from ESCs - The first method: generation of MMPs from ESCs and their differentiation into myogenic cells - Isolation of MMPs - Differentiation into skeletal myoblasts - The second method: EB generation and differentiation into skeletal muscle - Formation of EBs - Differentiation of EBs into skeletal myoblasts • Protocols for myogenic cell induction from iPSCs • Mouse and human-pluripotent derived myocytes as an in vitro model of MDs • Therapeutic development based on ESC- or iPSC-derived cells • Conclusion Muscular dystrophies (MDs) are a heterogeneous group of inherited disorders characterized by progressive muscle wasting and weakness likely associated with exhaustion of muscle regeneration potential. At present, no cures or efficacious treatments are available for these diseases, but cell transplantation could be a potential therapeutic strategy. Transplantation of myoblasts using satellite cells or other myogenic cell populations has been attempted to promote muscle regeneration, based on the hypothesis that the donor cells repopulate the muscle and contribute to its regeneration. Embryonic stem cells (ESCs) and more recently induced pluripotent stem cells (iPSCs) could generate an unlimited source of differentiated cell types, including myogenic cells. Here we review the literature regarding the generation of myogenic cells considering the main techniques employed to date to elicit efficient differentiation of human and murine ESCs or iPSCs into skeletal muscle. We also critically analyse the possibility of using these cellular populations as an alternative source of myogenic cells for cell therapy of MDs. © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.