(I-338) Tissue Engineered Muscle in Microgravity for Studying Sarcopenia and Drug Screening

Introduction:: Skeletal muscle undergoes age-related muscle atrophy known as sarcopenia. Efforts to develop drugs treat sarcopenia are hindered by its slow progression. Given the unique qualities of microgravity to accelerate the process of aging and muscle disuse, we hypothesized that engineered skeletal muscle in microgravity mimics sarcopenia as an accelerated platform of sarcopenia.


Materials and Methods:: Engineered muscle was formed by culturing human muscle progenitor cells (MPCs) onto immobilized strips of anisotropic nanofibrillar collagen scaffold. The muscles were flown to the International Space Station and then cultured in differentiation media consisting of 2% horse serum for up to 7 days. Insulin-like growth factor-1 (IGF-1) or a prostaglandin dehydrogenase (PDGH) inhibitor were also added to the differentiation media for 7 days to assess for drug effects. At time points up to 7 days, samples were collected for RNA Sequencing. The same experiments were performed in regular gravity conditions as controls.


Results, Conclusions, and Discussions:: In comparison to engineered muscle cultured in normal gravity conditions, engineered muscle in microgravity showed an induction of oxidative stress and muscle stem cell dysfunction that was consistent with aging and sarcopenia, based on RNA sequencing. Gene set enrichment analysis showing significantly upregulated pathways such as oxidative stress-induced senescence. Conversely, significantly downregulated pathways included those involved in notch and Wnt signaling. IGF-1 and a PDGH inhibitor could partially reverse the effects of microgravity.

These data demonstrate that engineered muscle in microgravity is a powerful accelerated platform of muscle aging/disuse and has the potential for drug screening applications in the future.




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