猪iPS细胞移植治疗猪心肌梗死模型的应用研究

Application of swine iPS cell transplantation in porcine myocardial infarction model

目的利用转缝隙连接蛋白43／闭锁小带．1（CX43／ZO-1）双基因诱导多能干细胞（iPS细胞）移植猪心肌梗死模型观察对梗死心肌的治疗效果。方法利用球囊堵塞前降支法建立猪心肌梗死模型，1周后冠脉内分别注射1640培养基（安慰剂组）、转CX43的iPS细胞、转CX43／ZO-1基因ips细胞；3个月后使用免疫电子显微镜及心脏彩超技术评价疗效。结果转CX43／ZO-1基因iPS组与安慰剂组和转CX43的iPS组相比，电子显微镜下可见梗死区与正常心肌交界区可见到大量岛状心肌细胞、血管及完整的闰盘结构，心脏彩超示左心室舒张末期内径缩小，射血分数明显提高（P〈0．05）。结论转CX43／ZO-1双基因ips细胞可促进猪心肌梗死模型心肌细胞再生及心功能恢复。

Objective To observe the therapeutic effect of porcine myocardium against porcine my- ocardial infarction （MI） by porcine myocardial infarction model with connexin-43/zonula occludens-1 （CX43/ZO-1） double gene induced pluripotent stem cells （iPS） transplantation. Methods Porcine myo- cardial infarction model was established by balloon occlusion. One week later, 1640 culture medium, CX43 gene ips cells and CX43/ZO-1 gene ips cells were injected into the different coronary arteries. After 3 months, electron microscopy and color Doppler ultrasonography were used to evaluate the curative effect. Results Compared to ips group of CX43 and 1640 culture group, in CX43/ZO-1 gene ips group, electron microscope showed a large number of island-like cardiomyocytes, blood vessels and intact intercalated discs in the infarct area and normal myocardial junction area structure, color Doppler echocardiography showed left ventrieular end diastolic diameter reduced, and ejection fraction was significantly increased （P 〈 0. 05）. Conclusions Transfection of CX43/ZO-1 double gene ips cells can promote cardiomyocyte regen- eration and cardiac function recovery in porcine myocardial infarction model.