The emergence of human pluripotent stem cell (hPSC) technology over the past two decades has provided a source of normal and diseased human cells for a wide variety of in vitro and in vivo applications. Notably, hPSC-derived cardiomyocytes (hPSC-CMs) are widely used to model human heart development and disease and are in clinical trials for treating heart disease. The success of hPSC-CMs in these applications requires robust, scalable approaches to manufacture large numbers of safe and potent cells. Although significant advances have been made over the past decade in improving the purity and yield of hPSC-CMs and scaling the differentiation process from 2D to 3D, efforts to induce maturation phenotypes during manufacturing have been slow. Process monitoring and closed-loop manufacturing strategies are just being developed. We discuss recent advances in hPSC-CM manufacturing, including differentiation process development and scaling and downstream processes as well as separation and stabilization.
Keywords: bioreactors; cardiomyocytes; hPSC; human pluripotent stem cells; manufacturing; quality attributes; scale-up; stem cells.