Hypoxic culture enhances the expansion of rat bone marrow-derived mesenchymal stem cells via the regulatory pathways of cell division and apoptosis

作者：Zhang, Jun; Xiong, Lei; Tang, Wenxian; Tang, Lin; Wang, Baohe^*

来源：In Vitro Cellular & Developmental Biology-Animal, 2018, 54(9): 666-676.

DOI：10.1007/s11626-018-0281-3

• Hypoxia
• Mesenchymal stem cell
• Proliferation
• Rat

This study aimed to examine the proliferative behavior and molecular mechanisms of rat bone marrow-derived MSCs (rBMSCs) cultured under three different oxygen concentrations. Passaged rBMSCs exhibited significantly greater proliferation rates at 1% O-2 and 5% O-2 than those at 18% O-2 and the cells exposed to 1% O-2 showed the highest proliferative potential, which was evidenced by the growth curves, colony-forming efficiencies, and CCK-8 absorbance values. The rBMSCs grown under hypoxic culture conditions (1% O-2 and 5% O-2) had the increased percentage of cells in S + G(2)/M-phase and the decreased apoptotic index, compared with normoxia (18% O-2). It was revealed for the first time that there were more phosphohistone H3 (PHH3)positive cells and higher expressions of proliferating cell nuclear antigen (PCNA) in the hypoxic cultures of rBMSCs than in the normoxic culture. Hypoxia upregulated the anti-apoptotic protein Bcl-2 and downregulated the pro-apoptotic proteins Bax and the cleaved caspase-3 in cultured rBMSCs. The levels of hypoxia-inducible factor-1 alpha (HIF-alpha) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) were increased in the hypoxic-cultured rBMSCs. Nevertheless, no significant difference was observed in p53 level of rBMSCs between different oxygen concentrations. In conclusion, the hypoxia exerts a promoting effect on the in vitro expansion of rBMSCs via several signaling and molecular pathways involved in the control of cell cycle and apoptosis.

• 出版日期2018-10
• 单位湖南师范大学