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Abstract

In this talk, I will present our recent progress on engineering of highly functional cardiac and skeletal muscle tissues starting from human pluripotent stem cell derived cardiomyocytes or primary human skeletal muscle progenitors isolated from standard muscle needle biopsies. I will first describe engineering of functional human cardiac tissue patches and miniaturized tissue bundles aimed toward potential use in medium-throughput physiological, pharmacological, and toxicological studies as well as in the treatment of cardiac injury. The results of structural, molecular, and functional comparisons of human cardiomyocytes cultured in a 3D tissue-engineered hydrogel environment vs. standard 2D culture will be also presented. These studies have revealed that specific combinations of hydrogel composition, dynamic biochemical culture environment, boundary conditions imposed on cells, and supporting non-myogenic cell types can uniquely advance structural and electromechanical maturation of engineered myocardium to a level approaching that of adult heart tissue. I will then describe how building on work with rat cells, we for the first time engineered an electrically and chemically responsive, contractile human skeletal muscle tissue made of primary cells isolated from standard muscle biopsies. These human muscle tissues contain aligned cross-striated myofibers, maintain stem cell pool, exhibit physiological force-length and force-frequency relationships, and show expected responses to a variety of chemicals and drugs including extracellular calcium, caffeine, acetylcholine, clenbuterol, chloroquine, and different statins. Together, these results open doors to new studies of striated muscle function, disease, and regeneration, and provide preclinical human-based assays for testing of novel therapeutics.