An improper mechanical microenvironment may be a barrier to efficient differentiation of functional cardiomyocytes from human pluripotent stem cells (hPSCs). We used a polyacrylamide hydrogel system as a model to assess the effect of the mechanical microenvironment on cardiogenesis over a physiologic range of substrate stiffness. We cultured hPSCs in both embryoid bodies and undifferentiated monolayer cultures on the different stiffness hydrogels, then differentiated the monolayers via temporal exposure to small molecules that upregulate then downregulate the Wnt signaling pathway. Using this model, both culture systems exhibited a stiffness-dependent trend where cardiogenesis peaked at a physiologically-relevant stiffness. Subsequent experiments with small molecule inhibitors of mechanosensing pathways suggested that substrate stiffness can �prime� hPSCs for differentiation. Our approach to studying the effects of the mechanical microenvironment using a hydrogel system may uncover molecular targets to modulate for efficient cardiogenesis.

Exploring signaling for stiffness-dependent differentiation of cardiomyocytes from human pluripotent stem cells

245th National Meeting (2013)

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