Bone marrow-derived mesenchymal stem cells in fibrin augment angiogenesis in the chronically infarcted myocardium.

Bone marrow-derived mesenchymal stem cells in fibrin augment angiogenesis in the chronically infarcted myocardium.
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DOI:
10.2217/rme.09.32
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发表时间:
2009-07
影响因子:
2.7
通讯作者:
Lee RJ
Lee RJ
中科院分区:
工程技术4区
文献类型:
--
作者:
Huang NF;Lam A;Fang Q;Sievers RE;Li S;Lee RJ

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目前治疗心肌梗死的努力包括细胞和基质支架的递送。骨髓间充质干细胞(BM-MSC)是分泌血管生成生长因子的多能干细胞,纤维蛋白已被证明是为细胞和组织提供结构支持的生物材料。本研究的目的是表征BM-MSCs在体外纤维蛋白中的附着和活力,然后评估用BM-MSCs在纤维蛋白中治疗促进慢性梗死心肌中新生血管形成的功效。将BM-MSC在纤维蛋白中培养,并分别通过使用肌动蛋白丝的免疫荧光染色和Live/Dead®活力测定来评估细胞附着和活力。为了确定BM-MSC在体内纤维蛋白中的功效,用细胞、纤维蛋白中的细胞、纤维蛋白或盐水处理慢性梗塞的大鼠心脏(n = 9)。5周后,评估梗死瘢痕组织的新血管形成。骨髓间充质干细胞在体外纤维蛋白中培养时表现出强大的细胞附着和活力。此外,当一起注射到梗死组织中时,与分别用细胞或纤维蛋白处理相比,纤维蛋白中的BM-MSC可以通过增加毛细血管密度来增强新血管形成。伴随着毛细血管密度的显著改善,梗死瘢痕中VEGF水平增加。本研究证明了BM-MSCs和纤维蛋白联合递送的血管生成潜力,并强调了干细胞-基质方法用于心肌修复的优势。
Current efforts to treat myocardial infarction include the delivery of cells and matrix scaffolds. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells that secrete angiogenic growth factors, and fibrin has been shown to be a biomaterial that provides structural support to cells and tissues. The objective of this study was to characterize the attachment and viability of BM-MSCs in fibrin in vitro, and then to assess the efficacy of treatment with BM-MSCs in fibrin for promoting neovascularization in the chronically infarcted myocardium. BM-MSCs were cultured in fibrin and assessed for cell attachment and viability by using immunofluorescence staining for actin filaments and Live/Dead® viability assays, respectively. To determine the efficacy of BM-MSCs in fibrin in vivo, chronically infarcted rat hearts were treated with either cells, cells in fibrin, fibrin or saline (n = 9). After 5 weeks, the infarct scar tissues were assessed for neovascularization. BM-MSCs exhibited robust cell attachment and viability when cultured in fibrin in vitro. Furthermore, when injected together into the infarcted tissue, BM-MSCs in fibrin could enhance neovasculature formation by increasing capillary density, in comparison to treatment by cells or fibrin separately. Concomitant to significant improvement in capillary density was an increase in the levels of VEGF in the infarct scar. This study demonstrates the angiogenic potential of the combined delivery of BM-MSCs and fibrin, and highlights the advantage of stem cell-matrix approaches for myocardial repair.
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