人脐血间充质干细胞抑制心肌细胞凋亡的作用与安全性

Safety and inhibitory effect of umbilical cord blood-derived mesenchymal stem cells on cardiomyocyte apoptosis

目的探讨人脐带血来源的间充质干细胞(mesenchymal stem cells,MSCs)诱导后的安全性及其与人心肌细胞共培养下的抗凋亡作用。方法在知情同意的原则下,取得10位供者分娩时的脐带血。脐带血来源的MSCs经5-氮杂胞苷处理后向心肌细胞诱导分化。观察诱导分化的MSCs端粒酶活性,G带显带技术下的染色体组型,裸鼠体内诱导肿瘤形成,RT-PCR以及共培养下对心肌细胞凋亡的抑制作用。结果脐带血来源的MSCs可在体外经5-氮杂胞苷诱导分化为心肌细胞,诱导后的细胞具有端粒酶活性,未观察到异常的染色体组型。p53、cyclinA、Cdk2、β-肌动蛋白、c-fos、h-TERT和c-myc在5-氮杂胞苷处理前后的MSCs中表达相似。注射到裸鼠体内未见肿瘤形成。脐带血来源的MSCs对人心肌细胞凋亡有明显的抑制作用。结论脐带血来源的MSCs是一种安全有效的移植治疗的细胞来源,共培养下能抑制人心肌细胞的凋亡。

Objective To study the safety and apoptosis inhibition of the umbilical cord blood （UCB）-derived mesenchymal stem cells（MSCs） co-cultured with human cardiomyocytes. Methods UCB was collected from 10 donors at the time of delivery with informed consent. The UCB-derived MSCs were treated with 5-AZA and induced to differentiate into cardiomyocytes. The telomerase activity, G-banding patterns of chromosomal karyotypes, tumor formation in nude mice, RT-PCR,and the apoptosis inhibition effect of UCB-derived MSCs were investigated. Results MSCs derived from UCB could be differentiated into cardiomyocytes in vitro after 5-AZA induction. The induced cells possessed telomerase activity and no abnormal chromosomal karyotypes were observed. Expression of p53, cyclinA, Cdk2,β-actin, c-los, h-TERT and c-myc was similar in MSCs before and after 5-AZA treatment. There was no tumor formation after the cells were injected into nude mice. UCB-derived MSCs significantly inhibited apoptosis of human cardiomyocytes. Conclusion UCB-derived MSCs are a valuable safe and effective source for cell-transplantation treatment,and can inhibit the apoptosis of human cardiomyocytes in co-culture with it.