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人心脏瓣膜衍生支架可改善心肌梗死后小鼠模型的心脏修复。

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

机构信息

Laboratory of Cardiovascular Sciences, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China.

Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China.

出版信息

Sci Rep. 2017 Jan 4;7:39988. doi: 10.1038/srep39988.

Abstract

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.

摘要

使用生物材料进行心脏组织工程学,结合或不结合干细胞治疗,为修复梗死心脏提供了一种新的选择。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不能模拟天然心肌细胞外基质的生化成分和结构特性。在这里,我们假设人心脏瓣膜衍生支架(hHVS)作为一种临床相关的新型生物材料,可以为心脏修复提供天然心肌细胞外基质的适当微环境。在这项研究中,我们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 hHVS 上固定后,梗死后的小鼠骨髓 c-kit+细胞表现出体外增殖和心肌生成分化的能力增加。当用于在心肌梗死的小鼠模型中修复梗死心脏时,hHVS 单独植入或 c-kit+细胞接种 hHVS 均显著改善心功能并减少梗死面积;而 c-kit+细胞接种 hHVS 甚至优于 hHVS 单独使用。因此,我们成功地开发了用于心脏修复的 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临床相关证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1816/5209673/355f03c11288/srep39988-f1.jpg

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