经冠状动脉移植骨髓间质干细胞治疗心肌梗死的实验研究  

Transcoronary Implantation of Bone Marrow Stromal Cells Improves Heart Function After Myocardial Infarction

作　　者：杨国胜[1] 杨跃进[1] 白东峰[2] 杨伟宪[1] 高润霖[1] 陈在嘉[1] 

机构地区：[1]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院冠心病诊治中心,北京市100037 [2]中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院超声科,北京市100037

出　　处：《中国循环杂志》2007年第1期20-23,共4页Chinese Circulation Journal

摘　　要：目的:观察经冠状动脉输注骨髓间质干细胞移植的疗效。方法:成年犬21只,分为对照组(n=12)与移植组(n=9)。结扎冠状动脉左前降支后,移植组于冠状动脉内注入经标记的自体骨髓间质干细胞悬液,对照组仅注入培养基。6周后,对比病理、超声心动图及血流动力学指标的变化。结果:骨髓间质干细胞培养两周可增殖达5．0×107个细胞,移植前经4’,6-二脒基-2-苯吲哚(DAPI)染色后的标记阳性率近100％。移植6周后梗死区内可见DAPI标记阳性的细胞,其α肌动蛋白(α-actin)(+),并与周围的宿主细胞形成缝隙连接,Connexin43(+)。每个高倍视野(0．2 mm2)的瘢痕区毛细血管的数量,移植组显著高于对照组[(5．49±0．50)支比(2．03±0．46)支,P<0．01]。6周时移植组与对照组相比,左心室压力最大上升及下降速率(±dp／dtmax)及心输出量均显著上升[其数值分别为(3 057±1 246)mmHg／s比(1 569±618)mmHg／s,P<0．05;(3 107±1 031)mmHg／s比(1 465±647)mmHg／s,P<0．01;(1．88±0．28)L／min比(1．41±0．29)L／min,P<0．01],左心室射血分数显著提高(0．48±0．09比0．35±0．05,P<0．01)。实验中未发现明显的不良反应发生。结论:经冠状动脉输注骨髓间质干细胞移植,能够分化为心肌样细胞,促进梗死区新血管形成并改善心脏功能。Objective： To test the therapeutic effectiveness of transcoronary implanted stromal cells using a canine model. Methods： The canine acute coronary occlusion model was created by ligating the left anterior descending artery （LAD）. After LAD ligation, bone-marrow derived stromal cells were injected into the ligated coronary artery. Results： Six weeks later, lots of 4＇ ,6-Diamidino-2-phenyindole （DAPI） labelled stromal cells were identified in the scar tissue, expressing myogenic-specific protein of α-actin. Some stromal cells were found to be connected to the adjacent host cardiomyocytes with gap junction （ connexin 43 staining positive）. Cardiac function was evaluated by echocardiography at 6 weeks after implantation. Left Ventricular Ejection Fraction （LVEF） was improved（0. 48±0. 09 vs 0. 35±0.05, P 〈 0. 01 ）. The hemodynamic parameters including ± dp/dtmax and cardiac output were increased in the cell therapy group （P 〈 0. 05 ）. Stromal cell transplantation induced angiogenesis in the scar, and the number of capillary vessels per high-power field （0. 2mm^2 ） in the cell therapy group was 5.49±0. 50 （ and 2.03 ±0.46 for control group, P 〈0. 01 ）. Conclusions： This study demonstrated for the first time that bone-marrow stromal cell delivered via coronary artery are capable of targeted migration, differentiation into cardiomyocytes in the scar tissue and improvement of heart function.

关 键 词：间质干细胞 移植 心肌梗塞 心力衰竭 

分 类 号：R541.4[医药卫生—心血管疾病]