37 - Experimental and computational analysis of cardiomyocyte generation from iPS cells via temporal modulation of Wnt signaling
University of Virginia
Regenerating heart muscle cells may improve cardiac function after remodeling, for instance post-heart attack. A study demonstrated a highly efficient small molecule approach to differentiate human pluripotent stem cells (hPSCs) to functional cardiomyocytes. According to Lian et al. (2012), temporal modulation of the canonical Wnt signaling pathway with two small-molecule inhibitors achieved 98%-pure, functional cardiomyocytes after 15 days. We adapted this protocol to our feeder-free hPSC lines. After the first inhibitor treatment, cells expressed brachyury, a mesodermal marker, indicating they were developing along the cardiomyocyte pathway. A computational differential equation model was constructed to study the effects of temporal modulation on Wnt signaling. The results demonstrated that activation and subsequent inhibition of the Wnt pathway yielded cardiomyocytes; activation without inhibition did not. This suggests a hypothetical pathway linking sustained Wnt signaling with inhibition of cardiomyocyte development.