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即时骨髓间充质干细胞疗法可使急性心肌梗死的猪心脏功能早期恢复。

Prompt bone marrow-derived mesenchymal stem cell therapy enables early porcine heart function recovery from acute myocardial infarction.

作者信息

Fan Chang-Qing, Leu Steve, Sheu Jiunn-Jye, Zhen Yen-Yi, Tsai Tzu-Hsien, Chen Yung-Lung, Chung Sheng-Ying, Chai Han-Tan, Sun Cheuk-Kwan, Yang Jenq-Lin, Chang Hsueh-Wen, Ko Sheung-Fat, Yip Hon-Kan

机构信息

Division of Cardiology, Department of Internal Medicine, Xiamen Chang Gung Memorial Hospital.

出版信息

Int Heart J. 2014;55(4):362-71. doi: 10.1536/ihj.14-007. Epub 2014 Jun 25.

Abstract

Impact of early bone marrow-derived mesenchymal stem cell (BMDMSC) implantation on left ventricular (LV) function after AMI was studied.Twelve mini-pigs were equally divided into placebo (AMI through left coronary artery ligation) and cell-treated groups [BMDMSCs (3.0 × 10(7)) implanted into infarct area (IA)] with myocardium harvested by post-AMI day 90. Six healthy animals served as controls.On post-AMI day 90, magnetic resonance imaging showed a lower LV ejection fraction but higher LV dimensions in the placebo group (P < 0.003) that also had increased IAs but reduced wall thickness (P < 0.005). Pro-apoptotic gene expressions (Bax, caspase-3) and apoptotic nucleus number in IAs and peri-IAs were highest in the placebo group (P < 0.001). Inflammatory biomarker expressions (MMP-9, oxidized protein, CD40+ cells) were highest, whereas those of angiogenesis (VEGF, CD31+ cells, SDF-1α, CXCR4) and myocardium-preservation (connexin43, troponin-I, cytochrome-C) were lowest in the placebo group (P < 0.01).BMDMSC implantation preserved LV function and alleviated remodeling at post-AMI day 90.

摘要

研究了早期骨髓间充质干细胞(BMDMSC)植入对急性心肌梗死(AMI)后左心室(LV)功能的影响。将12只小型猪平均分为安慰剂组(通过左冠状动脉结扎造成AMI)和细胞治疗组[将BMDMSCs(3.0×10⁷)植入梗死区域(IA)],在AMI后第90天采集心肌。6只健康动物作为对照。在AMI后第90天,磁共振成像显示安慰剂组的左心室射血分数较低,但左心室尺寸较大(P<0.003),梗死区域也增大,但壁厚减小(P<0.005)。安慰剂组梗死区域和梗死周边区域的促凋亡基因表达(Bax、半胱天冬酶-3)和凋亡细胞核数量最高(P<0.001)。安慰剂组的炎症生物标志物表达(基质金属蛋白酶-9、氧化蛋白、CD40⁺细胞)最高,而血管生成(血管内皮生长因子、CD31⁺细胞、基质细胞衍生因子-1α、CXC趋化因子受体4)和心肌保护(连接蛋白43、肌钙蛋白I、细胞色素C)的表达最低(P<0.01)。BMDMSC植入在AMI后第90天保留了左心室功能并减轻了心脏重塑。

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