In vitro vascularization improves in vivo functionality of human engineered cardiac tissues

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Stem Cell Biology

Background:

• Engineered human cardiac tissues are promising for disease modeling and regenerative therapy.
• Successful in vivo engraftment of engineered cardiac tissues requires rapid vascularization and blood perfusion.
• Existing methods often struggle with long-term vascular stability and functional integration.

Purpose of the Study:

• To engineer highly functional, vascularized human cardiac tissues with stable capillary networks.
• To assess the in vitro and in vivo performance of these engineered tissues.
• To evaluate their potential for regenerative applications in cardiac repair.

Main Methods:

• Co-culture of human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) and endothelial cells (hiPSC-ECs) in optimized serum-free media.
• Long-term in vitro culture (4 weeks) to establish stable capillary networks.
• Implantation into dorsal-skinfold chambers in immunocompromised mice to assess in vivo vascularization and function.

Main Results:

• Vascularized cardiopatches maintained stable capillary networks for 4 weeks with high contractile stress and conduction velocity.
• Implanted tissues showed improved angiogenesis and lumenization, forming hybrid human-mouse capillaries.
• Implanted vascularized tissues exhibited enhanced conduction velocity and Ca2+ transient amplitude compared to avascular controls, with robust blood perfusion.

Conclusions:

• Successfully engineered vascularized human cardiac tissues maintain function long-term in vitro.
• In vivo implantation promotes angiogenesis and functional integration with host vasculature.
• These engineered tissues offer a promising platform for cardiac disease modeling and regenerative therapy.