低氧预处理诱导骨髓间充质干细胞Pim-1激酶高表达抑制细胞凋亡

BACKGROUND: Bone marrow mesenchymal stem cells have a low survival rate after implanted into the ischemic myocardium. However, hypoxia preconditioning (HPC) may enhance bone marrow mesenchymal stem cell proliferation and promote its survival rate. OBJECTIVE: To explore whether Pim-1 is involved in HPC protecting against apoptosis of bone marrow mesenchymal stem cells and the relevant mechanism.METHODS: Bone marrow mesenchymal stem cells were respectively subjected to HPC for 0, 6, 12, and 24 hours. The expression of Pim-1 and apoptosis-related genes were detected by RT-qPCR and western blot. Then, the best hypoxic preconditioning time was determined as 12 hours. Then, bone marrow mesenchymal stem cells were assigned to one of the following groups: control (without HPC), 12-hour HPC, 12-hour HPC+Pim-1 inhibitor groups. Flow cytometry analysis was used to detect the cell apoptosis, Transwell assay to analyze the cell migration ability in each group, and JC-1 kit to detect mitochondrial membrane potential. Animal models of myocardial infarction were established. One week after modeling, bone marrow mesenchymal stem cells were given via multi-point injection around the infarct zone of rats. Two weeks after modeling, heart tissues of rats were taken and sliced followed by DiI staining to calculate the survival rate of bone marrow mesenchymal stem cells. Additionally, rat cardiac function was assessed by echocardiography prior to and after modeling as well as at 4 weeks after cell transplantation. RESULTS AND CONCLUSION: At 12 hours after HPC, the expression of Pim-1, p-Akt and Bcl-2 gene in the infarct region was significantly increased, but the expression of caspase-3 and Bax was significantly decreased. Compared with the control group, cell viability in the 12-hour HPC group was increased very significantly at 1 week after cell transplantation (P < 0.001), the migration and anti-apoptosis ability were enhanced significantly (P < 0.01) and the cardiac function of rats was significantly improved in the 12-hour HPC group (P < 0.05). All of these protective effects were blocked by the Pim-1 inhibitor. These findings indicate that HPC can protect bone marrow mesenchymal stem cells from apoptosis through activating Akt and up-regulating Pim-1, and thereby improve the therapeutic effect of bone marrow mesenchymal stem cell transplantation on ischemic heart diseases.中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程 

Hypoxic preconditioning inhibits apoptosis of bone marrow mesenchymal stem cells through overexpressing Pim-1