不同月龄人脐带间充质干细胞移植梗死心肌的血运重建

Transplantation of human umbilical cord mesenchymal stem cells at different gestational age for myocardium revascularization after myocardial infarction

背景:干细胞移植有利于心肌梗死后的心肌血运重建及改善心功能,HLA-G分子在免疫耐受状态的形成及维持中具有重要作用。目的:观察不同月龄有HLA-G表达差异的人脐带间充质干细胞移植后对急性心肌梗死兔血运重建的影响。方法:健康新西兰大白兔30只,随机数字表法分为小月龄细胞移植组、足月龄细胞移植组及对照组。建立兔心肌梗死模型后2周,将小月龄人脐带间充质干细胞和足月人脐带间充质干细胞分别标记BrdU,多点注射心肌梗死的交界区和中心区,对照组注射无血清培养基。结果与结论:移植后4周,小月龄和足月龄细胞移植组在心肌梗死区均发现有BrdU示踪细胞,且两组梗死区心肌纤维化程度、心肌梗死面积均少于对照组(P<0.01),两移植组间差异也有显著性意义(P<0.05)。Ⅷ因子染色见小月龄细胞移植组毛细血管密度高于足月龄细胞移植组(P<0.01),且两移植组与对照组比较差异也有显著性意义(P<0.05)。提示HLA-G表达量较高的小月龄脐带间充质干细胞能更好促进梗死区血管新生,改善血运重建,有潜力成为心肌细胞移植的更理想来源。

BACKGROUND：Transplantation of stem cells has a beneficial effect on myocardium revascularization and improving cardiac function after myocardial infarction, and HLA-G protein contributes to the formation and maintenance of the immune tolerance. OBJECTIVE：To investigate the transplantation effects of human umbilical cord mesenchymal stem cells at different gestational age with different HLA-G expression levels on myocardium revascularization after myocardial infarction in rabbits. METHODS：Thirty healthy New Zealand rabbits were selected and were randomly divided into human smal gestational age umbilical cord-derived mesenchymal stem cells transplantation group, human ful-term umbilical cord-derived mesenchymal stem cells transplantation group and control group. After the rabbits models of acute myocardial infarction had been established, the former two groups were infused different umbilical cord-derived human umbilical cord mesenchymal stem cells labeled with 5-bromo-2-deoxyuridine into the edge and center of myocardial infarct region by multipoint injection. Rabbits in the control group were subjected to an equal volume of serum-free culture medium. RESULTS AND CONCLUSION：Four weeks after celltransplantation, 5-bromo-2-deoxyuridine-positive cells were found surrounding the infarct site in both transplantation groups. Myocardial fibrosis and myocardial infarct size were significantly lower in both transplantation groups than those of the control group （P〈0.05）, and there was a significant difference between the two transplantation groups （P〈0.01）. The positive staining of factor VII indicated that capil ary density was increased significantly in the smal gestational age umbilical cord-derived mesenchymal stem cells transplantation group as compared with the ful-term umbilical cord-derived mesenchymal stem cells transplantation group （P〈0.01）, and a sstatistical difference was found between two transplantation groups and the control group （P〈0.01）. Transplantation of human umbilical cord mesenchymal stem cells with high HLA-G expression increases new capil ary vessels and improves myocardium revascularization. Al indicate that human smal gestational age umbilical cord mesenchymal stem cells have the potential to become the better source of cardiomyocytes transplantation.