Engrafted Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Undergo Clonal Expansion In Vivo

Abstract

Preclinical studies have suggested that transplanted human pluripotent stem cell-derived cardiomyocyte (hPSC-CM) grafts expand due to proliferation. This knowledge came from cell cycle activity measurements that cannot discriminate between cytokinesis or DNA synthesis associated with hypertrophy. To refine our understanding of hPSC-CM cell therapy, we genetically engineered a cardiomyocyte-specific fluorescent barcoding system into an hPSC line. Since cellular progeny have the same color as parental hPSC-CMs, we could identify subsets of engrafted hPSC-CMs that clonally expanded, with the remainder being non-proliferative and hypertrophic.