Hypoxia enhances buffalo adipose-derived mesenchymal stem cells proliferation, stemness, and reprogramming into induced pluripotent stem cells
Hypoxia enhances buffalo adipose-derived mesenchymal stem cells proliferation, stemness, and reprogramming into induced pluripotent stem cells
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缺氧可增强水牛脂肪来源的间充质干细胞的增殖、干性和重编程为诱导多能干细胞。
DOI：
10.1002/jcp.28342
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发表时间：
2019-10-01
影响因子：
5.6
通讯作者：
Yang, Sufang
中科院分区：
文献类型：
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作者：
Deng, Yanfei;Huang, Guiting;Yang, Sufang
来自牲畜的脂肪组织来源的间充质干细胞（ASC）是动物繁殖和兽医治疗的宝贵资源。先前的研究表明，低氧条件有利于维持ASC的生理活性。然而，缺氧对水牛 ASC (bASC) 的影响仍不清楚。在这项研究中，研究了缺氧对 bASC 的增殖、干性和重编程为诱导多能干细胞 (iPSC) 的影响。结果表明，低氧培养条件（5%氧气）增强了bASC的增殖和集落形成。缺氧时增殖相关基因的表达水平以及碱性成纤维细胞生长因子（bFGF）和血管内皮生长因子（VEGF）的分泌显着增强。缺氧培养条件激活缺氧诱导因子1α（HIF-1α），从而促进bFGF和VEGF的分泌，进而增强HIF-1α的表达并促进bASC的增殖。此外，在低氧培养条件下，bASCs表现出间充质干细胞的主要特征，多能标志物OCT4、NANOG、C-MYC的表达水平以及bASCs的分化能力显着增强。最后，bASC 在低氧培养条件下更有效、更容易地重编程为 iPSC，并且这些 iPSC 表现出原始多能干细胞的一些特征。这些发现为阐明缺氧对 bASC 增殖、干性维持和重编程等生理活动的详细机制提供了理论指导。
Adipose tissue-derived mesenchymal stem cells (ASCs) from livestock are valuable resources for animal reproduction and veterinary therapeutics. Previous studies have shown that hypoxic conditions were beneficial in maintaining the physiological activities of ASCs. However, the effects of hypoxia on buffalo ASCs (bASCs) remain unclear. In this study, the effects of hypoxia on proliferation, stemness, and reprogramming into induced pluripotent stem cells (iPSCs) of bASCs were examined. The results showed that the hypoxic culture conditions (5% oxygen) enhanced the proliferation and colony formation of bASCs. The expression levels of proliferation-related genes, and secretion of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were significantly enhanced in hypoxia. Hypoxic culture conditions activated hypoxia-inducible factor-1 alpha (HIF-1 alpha), thereby contributing to the secretion of bFGF and VEGF, which in turn enhanced the expression of HIF-1 alpha and promoted the proliferation of bASCs. Furthermore, in hypoxic culture conditions, bASCs exhibited the main characteristics of mesenchymal stem cells, and the expression levels of the pluripotent markers OCT4, NANOG, C-MYC, and the differentiation capacity of bASCs were significantly enhanced. Finally, bASCs were more efficiently and easily reprogrammed into iPSCs in hypoxic culture conditions and these iPSCs exhibited some characteristics of naive pluripotent stem cells. These findings provide the theoretical guidance for elucidating the detailed mechanism of hypoxia on physiological activities of bASCs including proliferation, stemness maintenance, and reprogramming.