Abstract 1854: Endothelial Cell Co-culture Within Tissue Engineered Cardiomyocyte Sheets Enhances Neovascularization And Improves Cardiac Function Of Ischemic Hearts
Regenerative therapies including myocardial tissue engineering have been pursued as a new possibility to repair the damaged myocardium. We examined the effects of promoting neovascularization by controlling the densities of co-cultured endothelial cells (ECs) within tissue-engineered myocardial tissues created using our cell sheet-based tissue engineering approach. Neonatal rat cardiomyocytes were co-cultured with GFP(+) rat-derived endothelial cells on temperature-responsive culture dishes. Co-cultured ECs formed pre-vascular networks within cardiomyocyte sheets(Fig. A⇓). Co-cultured cell sheets preserving EC networks were harvested from the dishes only by lowering temperature and layered to create 3D myocardial tissues. These patch-like cardiac tissues were then transplanted onto infarcted rat hearts. Four weeks after transplantation, capillary densities of the EC(+) cardiac grafts was significantly higher than in EC(−) tissues (4×105 ECs, 137±5 vs. ECs(−), 56±6*; *p<0.01). Furthermore, blood vessels originating from the engineered EC(+) cardiac tissues, bridged to connect with capillaries of the host heart. Finally, by increasing EC densities, recovery of cardiac function after transplantation of the engineered tissues could be significantly improved (fractional shortening: sham, 14±2%; EC(−), 17±3%; 2×105 ECs, 17±3%; 4×105 ECs, 20±2%*; 8×105 ECs, 24±4%*; *p<0.05) (Fig. B⇓). In conclusion, we demonstrate that control of EC densities in engineered cardiac tissues induces enhanced neovascularization, and directly leads to improved function of ischemic myocardium.