Functional microvascularization of human myocardium in vitro

In this study, we report static and perfused models of human myocardial-microvascular interaction. In static culture, we observe distinct regulation of electrophysiology of human induced pluripotent stem cell derivedcardiomyocytes (hiPSC-CMs) in co-culture with human cardiac microvascular endothelial cells (hCMVECs) and human left ventricular fibroblasts (hLVFBs), including modification of beating rate, action potential, calcium handling, and pro-arrhythmic substrate. Within a heart-on-a-chip model, we subject this three-dimensional (3D) co-culture to microfluidic perfusion and vasculogenic growth factors to induce spontaneous assembly of perfusable myocardial microvasculature. Live imaging of red blood cells within myocardial microvasculature reveals pulsatile flow generated by beating hiPSC-CMs. This study therefore demonstrates a functionally vascularized in vitro model of human myocardium with widespread potential applications in basic and translational research.

Automated summary

This study presents static and perfused models of human myocardial-microvascular interaction. The co-culture of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) with human cardiac microvascular endothelial cells (hCMVECs) and human left ventricular fibroblasts (hLVFBs) showed distinct regulation of electrophysiology. A heart-on-a-chip model with microfluidic perfusion and vasculogenic growth factors successfully induced the spontaneous assembly of perfusable myocardial microvasculature. This study demonstrates a vascularized in vitro model of human myocardium with potential applications in basic and translational research.