Human heart valve-derived scaffold improves cardiac repair in a murine model of myocardial infarction.

Cardiac tissue engineering using biomaterials with or without combination of stem cell therapy offers a new option for repairing infarcted heart. However, the bioactivity of biomaterials remains to be optimized because currently available biomaterials do not mimic the biochemical components as well as the structural properties of native myocardial extracellular matrix. Here we hypothesized that human heart valve-derived scaffold (hHVS), as a clinically relevant novel biomaterial, may provide the proper microenvironment of native myocardial extracellular matrix for cardiac repair. In this study, human heart valve tissue was sliced into 100 μm tissue sheet by frozen-sectioning and then decellularized to form the hHVS. Upon anchoring onto the hHVS, post-infarct murine BM c-kit+ cells exhibited an increased capacity for proliferation and cardiomyogenic differentiation in vitro. When used to patch infarcted heart in a murine model of myocardial infarction, either implantation of the hHVS alone or c-kit+ cell-seeded hHVS significantly improved cardiac function and reduced infarct size; while c-kit+ cell-seeded hHVS was even superior to the hHVS alone. Thus, we have successfully developed a hHVS for cardiac repair. Our in vitro and in vivo observations provide the first clinically relevant evidence for translating the hHVS-based biomaterials into clinical strategies to treat myocardial infarction.

利用生物材料结合或不结合干细胞疗法的心脏组织工程为修复梗死心脏提供了一种新选择。然而，生物材料的生物活性仍有待优化，因为目前可用的生物材料既不能模拟天然心肌细胞外基质的生化成分，也不能模拟其结构特性。在此我们假设，人心脏瓣膜衍生支架（hHVS）作为一种具有临床相关性的新型生物材料，可能为心脏修复提供天然心肌细胞外基质的适宜微环境。在本研究中，通过冷冻切片将人心脏瓣膜组织切成100μm的组织薄片，然后进行脱细胞处理以形成hHVS。在贴附于hHVS上后，梗死后小鼠骨髓c - kit⁺细胞在体外表现出增殖能力和心肌分化能力增强。当用于在小鼠心肌梗死模型中修补梗死心脏时，无论是单独植入hHVS，还是植入接种了c - kit⁺细胞的hHVS，都显著改善了心脏功能并减小了梗死面积；而接种了c - kit⁺细胞的hHVS甚至优于单独使用hHVS。因此，我们成功开发了一种用于心脏修复的hHVS。我们的体外和体内观察结果为将基于hHVS的生物材料转化为治疗心肌梗死的临床策略提供了首个具有临床相关性的证据。