3D in vitro models of skeletal muscle: innovative approaches for animal science

Abstract

Skeletal muscle is organized into bundles of muscle fibers of different sizes and penetrated by vascular and nervous networks. Satellite cells are stem cells located along muscle fibers and are the basis of myogenic progenitors (myoblasts). Satellite cells can be easily extracted from muscle and cultured. Typical two-dimensional (2D) culture models of skeletal muscle-derived cells cannot fully recapitulate the organization and function of living muscle tissues, restricting their usefulness in in-depth physiological studies. The development of functional 3D culture models offer a major opportunity to mimic the living tissues and to model muscle diseases. In this respect, this new type of in vitro model significantly increases our understanding of the involvement of the different cell types present in the formation of skeletal muscle and their interactions, as well as the modalities of response of a pathological muscle to new therapies. This second point could lead to the identification of effective treatments. Here, we report the significant progress that has been made in recent years to engineer muscle tissue-like structures, providing useful tools to investigate the behavior of resident cells. Specifically, we were interested in the development of myopshere- and myobundle-based systems as well as bioprinting constructs. The electrical/mechanical stimulation protocols and the co-culture systems developed to improve tissue maturation processes and functionalities are presented. The formation of these biomimetic engineered muscle tissues represents a new platform for the study of skeletal muscle function and spatial organization in a large number of physiological and pathological contexts.