Hypoxia promotes proliferation and osteogenic differentiation potentials of human mesenchymal stem cells
Hypoxia promotes proliferation and osteogenic differentiation potentials of human mesenchymal stem cells
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DOI：
10.1002/jor.21517
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发表时间：
2012-02-01
影响因子：
2.8
通讯作者：
Lee, Oscar K.
中科院分区：
文献类型：
--
作者：
Hung, Shun-Pei;Ho, Jennifer H.;Lee, Oscar K.
骨髓间充质干细胞（Mesenchymal stem cells，MSCs）是一种存在于低氧环境中的干细胞。本研究的目的是探讨缺氧对间充质干细胞的影响，我们假设氧浓度调节细胞增殖和分化承诺之间的复杂平衡。在这项研究中，人骨髓来源的骨髓间充质干细胞培养在缺氧与1%O2。骨髓间充质干细胞缺氧培养7天后增殖能力增强。迁移实验显示缺氧可增强MSCs的迁移能力。此外，在低氧条件下，干性基因Oct4、Nanog、Sall4和Klf4的表达增加。此外，在4周的诱导期内，低氧条件下的MSC的分化能力有利于成骨，而脂肪形成受到抑制。细胞因子抗体芯片分析显示，低氧培养7 d后，多种生长因子表达上调，这些生长因子的差异表达可能是低氧条件下MSCs增殖和成骨能力增强的原因。总之，缺氧提供了一个有利的培养条件，以促进增殖，以及通过差异生长因子的产生，骨髓间充质干细胞的成骨。(C)2011年由Wiley Periodicals，Inc.出版的骨科研究学会。J Orthop Res 30：260266，2012
Mesenchymal stem cells (MSCs), which can be isolated from bone marrow and other somatic tissues, are residing in an environment with relative low oxygen tension. The purpose of this study is to investigate the effects of hypoxia on MSCs, and we hypothesize that oxygen concentration regulates the intricate balance between cellular proliferation and commitment towards differentiation. In this study, human bone marrow-derived MSCs were cultured under hypoxia with 1% O2. The proliferation ability of MSCs was increased after a 7-day hypoxic culture period. Migration assay showed that hypoxia enhanced the migration capabilities of MSCs. Moreover, expression of stemness genes Oct4, Nanog, Sall4 and Klf4 was increased under hypoxia. Furthermore, the differentiation ability of MSCs under hypoxia favored osteogenesis while adipogenesis was inhibited during a 4-week induction period. Cytokine antibody array analysis showed that a number of growth factors were up-regulated after a 7-day hypoxic incubation and the differential expression of growth factors may account for the increased proliferation and osteogenic potentials of MSCs under hypoxic condition. Taken together, hypoxia provides a favorable culture condition to promote proliferation as well as osteogenesis of MSCs through differential growth factor production. (C) 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:260266, 2012