低氧培养对间充质干细胞生物学的影响

背景：氧参与细胞内ATP的合成以供细胞代谢,氧浓度也是调节细胞生理功能的重要因素。骨髓间充质干细胞的生理病理活动是在低氧状态下进行,其发生机制还不完全清楚。目的：回顾分析低氧培养对间充质干细胞生物学的影响的研究进展。方法：应用计算机检索1997-01/2011-10 PubMed 数据库相关文章,检索词为“mesenchymal stem cells,hypoxia,HIF”;同时检索同期万方数据库、维普资讯网数据库和中国知网数据库相关文章,检索词“间充质干细胞,低氧培养,缺氧诱导因子”,共检索到文献1 120篇,最终纳入符合标准的文献48篇进行分析。结果与结论：低氧预处理的骨髓间充质干细胞凋亡率将降低,其作用机制是通过上调血管内皮生长因子表达、抑制p53凋亡信号的表达以及促进抗凋亡蛋白Bcl-2的高表达来降低细胞凋亡。低氧下骨髓间充质干细胞通过抑制WNT信号通路和骨形态发生蛋白信号通路等通路,增加损伤组织的增殖能力;缺氧组织可诱导间充质干细胞迁移至缺氧区域,参与此过程的主要信号通路包括：血管内皮生长因子信号通路、基质细胞衍生因子1信号通路以及c-Met信号通路;低氧可提高间充质干细胞的黏附性,主要通过诱导细胞骨架蛋白以及细胞间黏附分子的高表达而实现;缺氧下间充质细胞增加Angiopoietin-1和血管内皮生长因子等因子的表达来促进细胞分化。

Biological effects of hypoxia on mesenchymal stem cells

BACKGROUND:Oxygen is involved in the synthesis of ATP in cells for cellular metabolism, and the concentration of oxygen is also an important factor to control the physiological functions of cells. Physiological and pathological events of bone marrow mesenchymal stem cells always occur under hypoxia condition, but the mechanism is still unclear.OBJECTIVE:To overview the research progress of the biological effects of hypoxia on mesenchymal stem cells.METHODS:A computer retrieval of PubMed database, Wanfang database, Weipu database and CNKI database (1997-01/2011-10) was conducted to search the related articles with the keywords of “mesenchymal stem cells, hypoxia, hypoxia-induced factor” in English and Chinese. A total of 1 120 articles were retrieved, and finally 48 articles were included in final analysis according to the inclusion criteria.RESULTS AND CONCLUSION:Hypoxia induction could reduce the apoptosis of bone marrow mesenchymal stem cells by upregulating the expression of vascular endothelial growth factor and anti-apoptotic protein Bcl-2 and downregulating the expression of p53 apoptotic signaling. Hypoxia could increase the proliferation of bone marrow mesenchymal stem cells by inhibiting WNT signaling pathway and bone morphogenetic protein signaling pathway. Hypoxic tissue could induce the migration of mesenchymal stem cells to hypoxic region, the main signal pathways in this process include vascular endothelial growth factor signaling pathway, stromal cell-derived factor-1 signaling pathway and c-Met signaling pathway. Hypoxia could also increase the adhesion of mesenchymal stem cells mainly through the high expression of cytoskeletal proteins and cell-cell adhesion molecule. Hypoxia could promote cell differentiation by increasing the expression of angiopoietin-1 and vascular endothelial growth factor and other factors.