Development of a 96-well Platform for the Bulk Production of Three-Dimensional Human Skeletal Muscle Microtissues

Abstract

Skeletal muscle wasting is a largely untreatable condition wherein patients lose skeletal muscle strength, stamina, and protein content. We posit that the lack of skeletal muscle wasting treatments is due to the failings of existing skeletal muscle models. To address this problem, we developed a human muscle microtissue (hMMT) platform for bulk generation of reproducible, contractile, 3D hMMTs. hMMTs recapitulated key aspects of native human skeletal muscle, including muscle-specific protein expression, drug response, and contractility. Furthermore, the hMMT platform can non-invasively assess strength, and is exceedingly simple to fabricate. To illustrate hMMT platform utility, hMMTs were used with tumour-conditioned media to model cancer-associated muscle wasting in vitro. hMMTs were also used to screen chemotherapeutics, revealing that the drug irinotecan is toxic to human myofibers. Collectively, these results underline the considerable potential of the hMMT platform as a vehicle for skeletal muscle research and drug candidate validation.