背景:骨髓间充质干细胞可以分化为心肌细胞,促进血管再生,但在移植早期其自身分泌的细胞因子不足以维持良好的分化和再生.目的:验证腺病毒介导的肝细胞生长因子和血管内皮生长因子双基因转染新西兰兔骨髓间充质干细胞移植对新西兰兔梗死心肌组织的修复重建和血管再生的影响.方法:腺病毒介导肝细胞生长因子/血管内皮生长因子双基因转染BrdU 标记的新西兰兔骨髓间充质干细胞.取新西兰兔50只建立急性心肌梗死模型,4 周后随机分为5 组,分别于梗死心肌内注射:①骨髓间充质干细胞/Ad.血管内皮生长因子+肝细胞生长因子.②骨髓间充质干细胞/Ad.肝细胞生长因子.③骨髓间充质干细胞/Ad.血管内皮生长因子.④骨髓间充质干细胞.⑤对照组注射等量无血清IMDM培养液.移植4 周后观察移植细胞的分化和新生血管的形成,并通过超声多普勒检测心功能变化.结果与结论:除对照组外,其余4 组兔心功能都较移植前有明显改善(P < 0.05),其中移植双基因转染骨髓间充质干细胞/Ad.血管内皮生长因子+肝细胞生长因子组兔的心功能改善程度要明显高于其他3 组.部分BrdU 染色阳性的细胞可以分化成为内皮细胞,参与构成了梗死区域的新生毛细血管.与对照组比较,其余4 组都有明显的血管新生(P < 0.05),而以骨髓间充质干细胞/Ad.血管内皮生长因子+肝细胞生长因子组最显著.提示肝细胞生长因子/血管内皮生长因子双基因转染新西兰兔骨髓间充质干细胞移植于梗死心肌可以促进心肌再生和新生血管的形成,明显改善心功能.%BACKGROUND: The bone marrow mesenchymal stem cells (BMSCs) can differentiate into myocardial cells and promote angiogenesis. However, the cell factor excreted by BMSCs in the early period of transplantation could not promote the differentiation and regeneration. OBJECTIVE: To investigate the effects of BMSCs transplantation transfected by adenovirous mediated vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) gene therapy on the tissue repair and angiogenesis in rabbits with myocardial infarction. METHODS: Rabbit BMSCs were isolated, cultured and purified in vitro, then labeled with BrdU and transfected by adenovirus mediated VEGF and HGF gene. 50 rabbits were used to establish the acute myocardial infarction models. Four weeks later, 50 rabbit models were randomly divided into five groups: group A was injected with BMSCs/Ad.VEGF+HGF; group B was injected with BMSCs/Ad.HGF; group C was injected with BMSCs/Ad.VEGF; group D was injected with BMSCs; group E was control group, it was injected with the same concentration of serum-free IMDM medium. The differentiation and angiogenesis of BMSCs were observed at 4 weeks after transplantation. Doppler echocardiography was performed to detect the changes on heart function. RESULTS AND CONCLUSION: Except for control group, the heart function was obviously improved after transplantation in group A, B, C and D (P < 0.05), and the improvement was the best in A group. Some BrdU stained positive BMSCs could differentiate into the endothelial cells and incorporate into the coronary capillaries in the infracted region. Compared to the control group, the other four groups could facilitate the angiogenesis (P < 0.05), especially in the group A. BMSCs implantation combining with VEGF and HGF gene therapy can obviously promote the myocardial regeneration angiogenesis, and can improve the heart function.
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