Restoring anatomical complexity of a left ventricle wall as a step toward bioengineering a human heart with human induced pluripotent stem cell-derived cardiac cells

• DOI: 10.1016/j.actbio.2021.12.016
• Publication Date: 2021-12-20T08:01:54Z
• Authors: Camila Hochman-Me...; Fernanda C.P. Mes...; Jacquelynn Morrissey; Ernesto Curty da ...; Jorn Hulsmann; Karis Tang-Quan; Yutao Xi; Po-Feng Lee; Luiz C. Sampaio; Doris A. Taylor
• Keywords: Human heart

The heart is a highly complex, multicellular solid organ with energy-demanding processes that require dense vascular network, extensive cell-cell interactions, and extracellular matrix (ECM)-mediated crosstalk among heterogeneous cell populations. Here, we describe the regeneration of left ventricular (LV) wall using decellularized whole rabbit scaffolds recellularized exclusively human induced pluripotent stem cell-derived endothelial cells, cardiomyocytes, other cardiac types. Cells were sequentially delivered to scaffold an optimized cell:cardiomyocyte media. Macroscopic assessment after 60 days showed LV hearts was anatomically restored full thickness from base apex endocardium epicardium. Histologic analysis revealed pool cells containing aligned troponin T-positive in close contact ECM; vessels varied large artery-like, surrounded by smooth muscle actin+ capillary-like. Vessel patency demonstrated perfusion transplanted into femoral artery bed pig. construct exhibited visible beating responded chronotropic drug administration. These results demonstrate ability tissue engineer vascularized, full-thickness unparalleled level microanatomical organization composition, ECM STATEMENT OF SIGNIFICANCE: Decellularized (ECM) bioactive template for engineering, but recellularizing acellular challenging. successfully revascularized repopulated large, portion ventricle cells. At days, histologic studies cellular composition this region similar native heart. appropriately heartbeat-altering drugs. Vessels supported blood flow through surgically connected pig artery. findings move approach closer possibility clinical translation.