Cardiovascular progenitor cells (CPCs) expressing the ISL1-LIM–homeodomain transcription factor contribute developmentally to cardiomyocytes in all 4 chambers of the heart. Here, we show that ISL1-CPCs can be applied to myocardial regeneration following injury. We used a rapid 3D methylcellulose approach to form murine and human ISL1-CPC spheroids that engrafted after myocardial infarction in murine hearts, where they differentiated into cardiomyocytes and endothelial cells, integrating into the myocardium and forming new blood vessels. ISL1-CPC spheroid–treated mice exhibited reduced infarct area and increased blood vessel formation compared with control animals. Moreover, left ventricular (LV) contractile function was significantly better in mice transplanted with ISL1-CPCs 4 weeks after injury than that in control animals. These results provide proof-of-concept of a cardiac repair strategy employing ISL1-CPCs that, based on our previous lineage-tracing studies, are committed to forming heart tissue, in combination with a robust methylcellulose spheroid–based delivery approach.
Oscar Bartulos, Zhen Wu Zhuang, Yan Huang, Nicole Mikush, Carol Suh, Alda Bregasi, Lin Wang, William Chang, Diane S. Krause, Lawrence H. Young, Jordan S. Pober, Yibing Qyang
Cardiac differentiation of mouse ISL1 cardiovascular progenitor cell–derived spheroids (mISL1-CPC spheroids).