Maturation of Induced Pluripotent Stem Cell Derived Cardiomyocytes via Co-Culture with Supporting Cells of the Developing Heart

Authors

• IH Garcia-Pak
• W Li
• E Tampakakis
• Y Lin
• J Zou
• C Kwon
• Y Mukoyama

Abstract

The successful derivation of cardiomyocytes from human pluripotent stem cells, both embryonic and induced pluripotent stem cells (hiPSC), has opened up exciting possibilities for clinical applications such as tissue engineering, disease modeling, and drug toxicity testing. The hurdle in implementing such applications is that these cardiomyocytes are immature; they appear and behave like fetal cardiomyocytes. It has been shown that many cell types including endothelial cells, sympathetic neurons, and epicardium-derived fibroblasts and vascular smooth muscle cells associate with and provide signals to cardiomyocytes in the developing heart. In this study, we aim to overcome this limitation using co-culture of iPSC-derived cardiomyocytes (iPSC-CMs) to mimic the complex cell signaling found in the developing heart. We co-cultured epicardial cells and sympathetic ganglia isolated from mouse embryos with human umbilical vein endothelial cells and immature iPSC-CMs for 30 days. We examined whether these long-termed co-cultured iPSC-CMs exhibit a more mature morphology and up-regulation of cardiac genes highly expressed in the human adult cardiomyocytes. The co-culture condition has exhibited promising preliminary results in gene expression as well as cell structure that indicate greater maturity than in control conditions. We hope this co-culture system will benefit the field by providing a step forward in mature cardiomyocyte application and therapies.

Scientific Focus Area: Stem Cell Biology

This page was last updated on Friday, March 26, 2021