Abstract
Background: Heart disease is the leading cause of death in the world, requiring the development of novel and personalized therapeutic strategies for disease treatment. Heart tissue engineering holds a great promise for those therapies based on the reconstruction of patient-specific cardiac muscle. A bioartificial heart was reported by reseeding rat cardiomyocytes ( CMs ) into decellularized rat heart. Whether such method could be used to make human heart constructs remained unknown. Objectives: We sought to rebuild functional heart constructs using human induced pluripotent stem ( iPS) cells and decellularized whole mouse hearts. Methods: We repopulated decellularized mouse hearts with human iPS cell derived multipotential cardiovascular progenitors ( MCPs ). MCPs represent the earliest heart progenitors during human cardiogenesis and can give rise to multiple cardiovascular lineage cells. Results: The seeded MCPs differentiated in situ into CMs, smooth muscle and endothelial cells, which reconstructed the decellularized mouse hearts. The engineered constructs exhibited myocardium and vessel-like structures, contracted spontaneously with a rate of 40~50 beats/min, exhibited intracellular Ca2+ transients and responded as expected to various drug interventions. In addition, we found heart ECM could promote proliferation and myofilament formation of CMs from the repopulated human MCPs. Therefore this study established a novel strategy of human heart tissue engineering, which could be beneficial to study heart development, and future preclinical applications.
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