Kosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville, Louisville, KY, USA.
Department of Pharmacology & Toxicology, University of Louisville School of Medicine, Louisville, KY, USA.
Methods Mol Biol. 2021;2191:151-169. doi: 10.1007/978-1-0716-0830-2_10.
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.
将细胞递送到受损的心肌中会由于细胞大量死亡而导致有限的心脏再生。为了限制细胞死亡，我们的实验室将三维基质设计为细胞治疗的递送系统。我们的主要工作集中在由人诱导多能干细胞衍生的工程化心肌细胞形成工程化心脏组织 (ECT)。然而，ECT 的不成熟会阻碍其完全恢复受损的心肌。已经使用了各种调节方案，例如机械拉伸和/或电起搏，以激活成熟途径。为了提高 ECT 的成熟度，我们使用异源表达的光敏感通道蛋白转导素离子通道进行非接触式慢性光刺激。我们通过 AAV 包装的通道蛋白转导素转导 ECT，并在固有搏动率以上进行慢性光学起搏 (C-OP) 1 周，从而增加 ECT 的电生理特性。
