Development of Soft Substrate-Based In Vitro Muscle Models for Myokine Therapeutic Studies
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Sheng, Christina Y.
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Abstract
Though exercise is known to reduce the risks of various diseases, the underlying mechanism is largely unknown. In the last few decades, researchers have identified protein factors secreted by contracting skeletal muscle, termed myokines, that exert biological functions in the whole-body. Of all known myokines, however, only a small fraction has been studied and the majority of current in vitro myokine studies are conducted on hard plastic dishes, which limits the physiological relevance of the studies. Here, we utilized soft substrate-based muscle models to better understand the mechanisms underlying the protective effects of exercise and myokine. Frist, we developed soft in vitro muscle models and exercised the models to compare them with an in vivo mice exercise model. Then, as case studies, we investigated the protective effects of exercise and myokine on engineered muscles challenged with cancer cachexia or dexamethasone, a synthetic glucocorticoid commonly used as potent anti-inflammatory and immunosuppressive drugs but often leads to side effects, such as muscle atrophy. In vitro exercise models that better mimic in vivo exercise will serve as an important platform for future novel myokine-based drug discovery and studies.
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2024-12-02
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Dissertation (PhD)