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[肝细胞生长因子未增强骨髓间充质干细胞移植对猪急性心肌梗死模型心脏修复的作用]

[Hepatocyte growth factor did not enhance the effects of bone marrow-derived mesenchymal stem cells transplantation on cardiac repair in a porcine acute myocardial infarction model].

作者信息

Ma Dong-chao, Yang Zhi-jian, Wang Wei, Xu Shun-lin, Zhang Yu-Qing, Zhou Fang, Chen Bo, Xu Zhao-qiang, Cao Ke-jiang, Ma Wen-zhu

机构信息

Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2006 Feb;34(2):119-22.

Abstract

OBJECTIVE

To evaluate the impact of combined therapy with transplanting bone marrow-derived mesenchymal stem cells (BM-MSCs) via noninfarct-relative artery and hepatocyte growth factor (HGF) in a porcine myocardial infarction (MI) model.

METHODS

BM-MSCs were obtained from pig bone marrow, expanded in vitro with a purity of > 50%. MI was induced by ligating the distal left anterior descending artery in pigs. Eighteen animals received BM-MSCs cells (5 x 10(6)/ml, n = 6), BM-MSCs cells (5 x 10(6)/ml) plus HGF (4 x 10(9) pfu, n = 6) or equal volume culture medium (IMDM) via non-infarct-related artery at four weeks after MI. Gated myocardial perfusion imaging and coronary angiography were performed before and four weeks after transplantations. Histological examination was also performed 4 weeks after transplantation.

RESULTS

LVEF measured by gated myocardial perfusion imaging was similar among groups before transplantation and significantly increased in BM-MSCs (45 +/- 3 vs. 34 +/- 2%, P < 0.05) or BM-MSCs + HGF (46 +/- 6 vs. 34 +/- 3%, P < 0.05) treated animals while remained unchanged in IMDM (30 +/- 3 vs. 32 +/- 2%) treated animals 4 weeks post transplantation. Similarly, capillary density was also significantly higher and myocardial perfusion defect scores significantly decreased in BM-MSCs or BM-MSCs + HGF treated hearts than that in IMDM treated hearts. However, all these changes were similar between BM-MSCs and BM-MSCs + HGF groups. Rentrop score was similar before and 4 weeks after transplantation among various groups.

CONCLUSION

HGF in combination with BM-MSCs transplantation did not enhance the cardiac repair effects of BM-MSCs transplantation alone and BM-MSCs transplantation did not improve collateral circulation in this model.

摘要

目的

在猪心肌梗死(MI)模型中评估经非梗死相关动脉移植骨髓间充质干细胞(BM-MSCs)与肝细胞生长因子(HGF)联合治疗的效果。

方法

从猪骨髓中获取BM-MSCs,体外扩增后纯度>50%。通过结扎猪左前降支远端诱导MI。18只动物在MI后4周经非梗死相关动脉接受BM-MSCs细胞(5×10⁶/ml,n = 6)、BM-MSCs细胞(5×10⁶/ml)加HGF(4×10⁹ pfu,n = 6)或等体积培养基(IMDM)。在移植前和移植后4周进行门控心肌灌注成像和冠状动脉造影。移植后4周也进行组织学检查。

结果

移植前各组间通过门控心肌灌注成像测量的左室射血分数(LVEF)相似,移植后4周,接受BM-MSCs(45±3%对34±2%,P<0.05)或BM-MSCs+HGF(46±6%对34±3%,P<0.05)治疗的动物LVEF显著增加,而接受IMDM(30±3%对32±2%)治疗的动物LVEF无变化。同样,BM-MSCs或BM-MSCs+HGF治疗的心脏中毛细血管密度也显著更高,心肌灌注缺损评分显著低于IMDM治疗的心脏。然而,BM-MSCs组和BM-MSCs+HGF组之间所有这些变化相似。各组移植前和移植后4周的Rentrop评分相似。

结论

在该模型中,HGF与BM-MSCs移植联合并未增强单独BM-MSCs移植的心脏修复效果,且BM-MSCs移植未改善侧支循环。

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