UBC Theses and Dissertations
Cardiomyocyte differentiation with cyclic mechanical strain Zhao, Eric Jiahua
The creation of cardiomyocytes from pluripotent stem cells has the potential to revolutionize the treatment of heart disease, the discovery and testing of drugs, and our understanding of human physiology. Thus far, differentiation protocols have mainly focused on recapitulating the biochemical signalling events of cardiac organogenesis, and the resulting cardiomyocytes exhibit a fetal-like phenotype. We postulated that cyclic mechanical strain can mimic the mechanical environment of the developing heart, and, when applied in conjunction to biochemical differentiation protocols, can increase the efficiency of differentiation and the maturity of the resulting cells. Using an induced pluripotent stem cell line derived from human fibroblasts, we derived spontaneously contracting cardiomyocytes via treatment with activin A and bone morphogenetic protein 4 (BMP4). We observed that differentiation of induced pluripotent stem cells to cardiomyocytes is sensitive to cyclic strain, with the application of 5% continuous cyclic strain at 1Hz having the effect of inhibiting spontaneous contractions and disrupting sarcomere formation.
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