Human umbilical cord blood-derived mesenchymal stem cells inhibit cardiomyocyte apoptosis under co-culture conditions A safety and efficacy assessment / 中国组织工程研究

ABSTRACT

BACKGROUND: Umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) have been shown to lead to new tissue formation after homing and engrafting to the heart. But the safety of UCB-MSCs engrafting remains to be further investigated. OBJECTIVE: To study the safety and apoptosis inhibition of the UCB-MSCs under co-culture conditions on human cardiomyocytes. METHODS: UCB was collected at delivery with informed consent obtained from 10 donors. The UCB-MSCs were treated with 5-azaserine to induce differentiation into cardiomyocytes. The in vitro cultured cells of the 3rd-5~(th) passages and dividing cells were taken to detect telomerase activity, tumor-related gene expression, G-banding patterns of chromosomal karyotupes, cell surface antigen expression, tumor formation in nude mice, and inhibited apoptosis under co-culture conditions. RESULTS AND CONCLUSION: Prior to and after 5-azaserine induction, telomerase activity and tumor-related gene expression (p53, cyclin A, cdk2, β-actin, C-fos, h-TERT, c-myc) of UCB-MSCs were similar, no abnormal chromosomal karyotupes were observed, immunophenotype exhibited no change, CD34 was negative, but CD44 and CD90 (Thy-1) were positive. At 10 weeks after inoculation of UCB-MSCs, nude mice still survived healthily and no formed tumor in vivo was observed. Hematoxylin-eosin staining suggested normal subcutaneous tissue. Compared with simple cardiomyocytes, UCB-MSCs could significantly inhibit cardiomyocyte apoptosis under co-culture conditions (P < 0.05), indicating that human UCB-MSCs are a valuable, safe, and effective source of cell transplantation treatment.