3D micro-physiological systems for identification of therapeutic myokines

PROJECT SUMMARY Skeletal muscle is a highly vascularized tissue that can secrete cytokines and proteins, collectively termed as myokines. Despite the tremendous potential for translation, due to the dynamic nature of blood-borne factors, reliable identification of these humoral factors remains a major hurdle. To overcome this challenge, Dr. Jang and Dr. Park’s group will leverage advanced microengineering approaches to build a 3D microfluidic muscle circuit that can control mechanical and biochemical cues in the physiologically relevant 3D microenvironment. In this proposal, two groups will further refine and upgrade the in vitro muscle platform by integrating a cell-type-specific protein labeling system (MetRSL2774G transgene) to precisely identify the muscle secretome responsible for the muscle-to-remote organ communications. In addition, the team will also engineer an exercise-induced myokine reporter system using an optogenetic actuator (Channel-rhodopsin 2) co-expressed with protein labeling construct, MetRSL274G. Using these approaches, proposed studies will identify novel contraction-induced myokines that are responsible for the beneficial effects of exercise. Finally, the research team seeks to identify muscle proteomes that exert their action on muscle-heart crosstalk, especially in the context of ischemic preconditioning. The successful outcomes of this project will have far and broad implications in muscle biology and medicine. This minimally invasive 3D microphysiological system can be exploited in a variety of studies testing systemic tissue interactions. More importantly, upon validation, the experimental approach used in this proposal can be translated to develop myokine-based therapeutics for late-onset lifestyle disorders.