Alternative approaches to generating cardiomyocytes are under development

We would like to thank Masuda et al. for their interest in our recent review on induced pluripotent stem cells in relation to precision medicine (Chen, I.Y., Matsa, E., Wu, J.C. Induced pluripotent stem cells: at the heart of cardiovascular precision medicine. Nat. Rev. Cardiol. 13, 333-349; 2016).¹ In reading their correspondence, we agree that the current approaches to generating induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes (iPSC-CMs) can be both time-consuming and costly. Furthermore, the resultant cell products can exhibit batch-to-batch variations, making it sometimes difficult to interpret subtle phenotypic changes in iPSC-based applications, including drug screening, disease modeling, and regenerative therapy. Recent development of techniques to isolate, maintain, and significantly expand mouse and human induced cardiovascular progenitor cells (iCPCs) in culture has provided alternatives to produce cardiomyocytes that are potentially less heterogeneous than iPSC-CMs and in manners that are potentially less time-consuming and costly. We applaud Masuda et al. for discussing these promising techniques in their correspondence. For those interested in reading further on this topic, we gladly refer the readers to our recent editorial in Circulation Research entitled “Finding Expandable Induced Cardiovascular Progenitor Cells,”² which additionally discusses the necessary steps as well as hurdles for the clinical translation of expandable iCPCs.