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基于纤维蛋白贴片的胰岛素样生长因子-1基因修饰干细胞移植修复缺血心肌。

Fibrin patch-based insulin-like growth factor-1 gene-modified stem cell transplantation repairs ischemic myocardium.

作者信息

Li Jun, Zhu Kai, Yang Shan, Wang Yulin, Guo Changfa, Yin Kanhua, Wang Chunsheng, Lai Hao

机构信息

Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China Shanghai Institute of Cardiovascular Disease, Shanghai 200032, P.R. China.

Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.

出版信息

Exp Biol Med (Maywood). 2015 May;240(5):585-92. doi: 10.1177/1535370214556946. Epub 2015 Mar 11.

Abstract

Bone marrow mesenchymal stem cells (BMSCs), tissue-engineered cardiac patch, and therapeutic gene have all been proposed as promising therapy strategies for cardiac repair after myocardial infarction. In our study, BMSCs were modified with insulin-like growth factor-1 (IGF-1) gene, loaded into a fibrin patch, and then transplanted into a porcine model of ischemia/reperfusion (I/R) myocardium injury. The results demonstrated that IGF-1 gene overexpression could promote proliferation of endothelial cells and cardiomyocyte-like differentiation of BMSCs in vitro. Four weeks after transplantation of fibrin patch loaded with gene-modified BMSCs, IGF-1 overexpression could successfully promote angiogenesis, inhibit remodeling, increase grafted cell survival and reduce apoptosis. In conclusion, the integrated strategy, which combined fibrin patch with IGF-1 gene modified BMSCs, could promote the histological cardiac repair for a clinically relevant porcine model of I/R myocardium injury.

摘要

骨髓间充质干细胞(BMSCs)、组织工程心脏补片和治疗性基因都已被提出作为心肌梗死后心脏修复的有前景的治疗策略。在我们的研究中,用胰岛素样生长因子-1(IGF-1)基因修饰BMSCs,将其加载到纤维蛋白补片中,然后移植到猪缺血/再灌注(I/R)心肌损伤模型中。结果表明,IGF-1基因过表达可促进体外内皮细胞增殖和BMSCs向心肌样细胞分化。移植载有基因修饰BMSCs的纤维蛋白补片四周后,IGF-1过表达可成功促进血管生成、抑制重塑、提高移植细胞存活率并减少细胞凋亡。总之,将纤维蛋白补片与IGF-1基因修饰的BMSCs相结合的综合策略,可促进临床相关猪I/R心肌损伤模型的心脏组织学修复。

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