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Bioengineering skeletal muscle: how to build an intact human motor unit

R.J. Mills, School of Biomedical Sciences , The University of Queensland, St Lucia, QLD 4072, Australia.

In vitro three-dimensional culture systems are emerging as novel tools with which to study tissue development, organogenesis and stem cell behaviour ex vivo. These tissues promote higher levels of cell differentiation and tissue organisation and can recapitulate tissue-tissue interfaces and mechanical microenvironments of living organs; allowing the study of human physiology in an organ-specific context. We have developed a high-throughput micro-tissue screening platform that enables the culture of human skeletal muscle tissues in combination with human pluripotent stem cell-derived motor neurons; forming an intact motor unit. A fundamental advantage of this system is the ability to obtain real-time functional readouts; analysing active contractile force in a semi-automated manner. Bioengineering approaches can result in enhanced maturation and function of in vitro engineered skeletal muscle; recapitulating the features of an intact human skeletal muscle, as well as demonstrating the utility and screening capabilities of our platform.