Chronic optogenetic pacing of human-induced pluripotent stem cell-derived engineered cardiac tissues

Abstract

The delivery of cells into damaged myocardium induces limited cardiac regeneration due to extensive cell death. In an effort to limit cell death, our lab formulates three-dimensional matrices as a delivery system for cell therapy. Our primary work has been focused on the formation of engineered cardiac tissues (ECTs) from human-induced pluripotent stem cell-derived engineered cardiac cells. However, ECT immaturity hinders ability to fully recover damaged myocardium. Various conditioning regimens such as mechanical stretch and/or electric pacing have been used to activate maturation pathways. To improve ECT maturity, we use non-contacting chronic light stimulation using heterologously expressed light-sensitive channelrhodopsin ion channels. We transduce ECTs with an AAV packaged channelrhodopsin and chronically optically pace (C-OP) ECTs for 1 week above the intrinsic beat rate, resulting in increased ECT electrophysiological properties.