Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai, China.
J Cell Mol Med. 2017 Sep;21(9):1751-1766. doi: 10.1111/jcmm.13097. Epub 2017 Feb 28.
Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF-1α, Tβ4, VEGF and SDF-1 expression and decreased CXCL14 expression in hypoxic and serum-deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF-1α, Tβ4, VEGF, SDF-1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial-derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c-kit cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c-kit cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.
心脏贴片被认为是增强心肌梗死（MI）干细胞治疗的有前途的策略。然而，心脏贴片修复梗死心肌的潜在机制仍不清楚。在这项研究中，我们研究了载有 MSC 的 PCL/明胶贴片激活内源性心脏修复的机制。PCL/明胶贴片通过静电纺丝制成。该贴片增强了接种 MSC 的存活率及其 HIF-1α、Tβ4、VEGF 和 SDF-1 的表达，并降低了缺氧和无血清条件下 CXCL14 的表达。在小鼠 MI 模型中，分别检查了移植细胞贴片后植入 MSC 的存活和分布以及心外膜的激活。移植后 4 周，心脏功能明显改善。植入的 MSC 穿过心外膜并进入心肌。梗死心肌中 HIF-1α、Tβ4、VEGF、SDF-1 和 CXCL14 的表达趋势与体外表达相似。心外膜被激活，心外膜衍生细胞（EPDC）迁移到深层组织。EPDC 分化为内皮细胞和平滑肌细胞，一些 EPDC 表现出向心肌细胞分化的趋势。血液和淋巴管的密度显著增加。移植细胞贴片后，更多的 c-kit 细胞被募集到梗死的心肌中。这些结果表明，细胞贴片的心外膜移植通过增强移植细胞的存活率、加速局部旁分泌，从而激活心外膜并募集内源性 c-kit 细胞，促进梗死心肌的修复并改善心脏功能。细胞贴片的心外膜移植可能作为一种新的有效的 MI 治疗方法得到应用。
