Functional microvascularization of human myocardium in vitro

Area of Science:

• Cardiovascular Research
• Stem Cell Biology
• Bioengineering

Background:

• Understanding human myocardial-microvascular interactions is crucial for cardiovascular research.
• Existing in vitro models often lack the complexity of native cardiac microvasculature.

Purpose of the Study:

• To develop a functional in vitro model of human myocardium with integrated microvasculature.
• To investigate the electrophysiological effects of co-culturing cardiomyocytes with endothelial cells and fibroblasts.
• To assess the perfusability and vascularization of the engineered cardiac tissue.

Main Methods:

• 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).
• Utilized a heart-on-a-chip model with microfluidic perfusion and vasculogenic growth factors.
• Live imaging techniques to observe red blood cell flow within the engineered microvasculature.

Main Results:

• Distinct regulation of hiPSC-CM electrophysiology observed in co-culture, including changes in beating rate and action potential.
• Successful spontaneous assembly of perfusable myocardial microvasculature within the 3D co-culture.
• Demonstrated pulsatile blood flow within the engineered microvasculature, driven by beating hiPSC-CMs.

Conclusions:

• The study presents a functionally vascularized in vitro model of human myocardium.
• This model offers significant potential for advancing basic and translational cardiovascular research.
• The engineered tissue mimics key aspects of native myocardial-microvascular interactions.