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
Division of Cardiology, Department of Internal Medicine, Xiamen Chang Gung Memorial Hospital.
Int Heart J. 2014;55(4):362-71. doi: 10.1536/ihj.14-007. Epub 2014 Jun 25.
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.
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。