Advanced models of human skeletal muscle differentiation, development and disease: 3D cultures, organoids and beyond


The organization and function of living muscle tissues cannot be fully recapitulated by typical two-dimensional (2D) culture methods in skeletal muscle-derived cells, reducing their use in extensive physiological research. The development of a 3D culture model gives a significant potential for imitation of the live tissues and for modeling muscular disorders. This novel in vitro model enhances our awareness of the many cell kinds present in the development and interactions of skeletal muscle and of the methods by which a diseased muscle responds to new treatments.


In the review, the authors begin a brief summary of the production and differentiation of skeletal myogens, followed by a discussion with human biopsy-derived myoblasts (primary or immortalized) or pluripotent stem cells on current developments. They then explore approaches to build physiologically complicated models which provide clinically meaningful phenotypic readings, which may be utilized as results measurements for the development of therapy, with their viewpoint on the future in vitro skeleton muscle models.


The author states that “Advanced in vitro models of human skeletal muscle tissue are increasingly needed to model complex developmental dynamics and disease mechanisms not recapitulated in animal models or in conventional monolayer cell cultures.

There has been impressive progress towards creating such models by using tissue engineering approaches to recapitulate a range of physical and biochemical components of native human skeletal muscle tissue. In this review, we discuss recent studies focused on developing complex in vitro models of human skeletal muscle beyond monolayer cell cultures, involving skeletal myogenic differentiation from human primary myoblasts or pluripotent stem cells, often in the presence of structural scaffolding support.

We conclude with our outlook on the future of advanced skeletal muscle three-dimensional cultures (e.g. organoids and biofabrication) to produce physiologically and clinically relevant platforms for disease modeling and therapy development in musculoskeletal and neuromuscular disorders.”


Jalal S, Dastidar S, Tedesco FS. Advanced models of human skeletal muscle differentiation, development, and disease: Three-dimensional cultures, organoids and beyond. Curr Opin Cell Biol. 2021 Aug 9;73:92-104. DOI: 10.1016/ Epub ahead of print. PMID: 34384976.

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