低氧对间充质干细胞的影响.doc

1 低氧对间充质干细胞的影响【摘要】氧对于几乎所有的生命都是必需的, 它维持能量代谢及细胞的功能, 但机体多种细胞是处于生理或病理性低氧状态中,而体外细胞实验一般是在 20 %氧浓度下进行, 并不符合生理状态。直到最近, 关于低氧对于间充质干细胞( mesenchymal stem cells, MSC )的影响有了一系列的研究。体外实验表明, 适度低氧下 MSC 的生长和存活能力更好,氧浓度可以影响 MSC 向成骨、成软骨、成脂的分化倾向,低氧能提高特异性受体和配体相结合所介导的迁移。低氧可影响胚胎干细胞、造血干细胞、神经干细胞的生理学特性也是一证据。干细胞对缺氧反应的分子机制主要涉及低氧诱导因子拟1 (hypoxic inducible factor 拟1, HIF 拟 1)信号通路。本文综述了低氧对 MSC 的存活、增殖、分化和迁移的影响,以及涉及 HIF 拟1 等的分子机制。【关键词】低氧; 间充质干细胞; 细胞增殖; 细胞分化; 细胞迁移 Effect of Hypoxia on Mesenchymal Stem Cells 2 —— Review Abstract Oxygen is issential for life , but cultivation of cells is usually performed under 20% O2 , that do not replicate normal physiological hypoxia or pathological hypoxia conditions in the body. Recently, the effect of hypoxia on mesenchymal stem cells (MSCs) has been studied, under physiological hypoxia, MSCs thrive well, and the ability differentianing to osteoblast, chondrocyte and adipocyte as well as the ability of migration are changed. Hypoxia changes the physiological characteristics of embryonic stem cell, hematopoietic stem cell and neuron stem cell as well. The mechanism of these responses might be primarily involved in the hypoxic inducible factor 拟1 (HIF 拟 1) signal pathway. This review emphasizes that hypoxia is an important factor on all major aspects of stem cell biology including survival, proliferation, differentiation, and migration, and the mechanism involved in HIF 拟1 signaling pathway behind these responses was also discussed. Key words hypoxia; mesenchymal stem cell; cell proliferation; cell differentiation; cell migration 3 间充质干细胞( mesenchymal stem cells , MSC )具有强大的自我更新及多系分化潜能, 体内移植后可以迁移至损伤的部位( 多数为缺血缺氧的环境) 修复相应的组织。干细胞体外增殖分化的研究通常是在 20% O2 的条件下,然而体内氧浓度显著低于此值, 动脉血氧浓度约为 12% , 组织的平均氧浓度约为 3%, MSC 的主要积聚部位拟骨髓的氧浓度为 1%-7%, 富集干细胞的胚体氧浓度更低,而且处于一种动态变化之中。通常所谓的低氧更符合生理状态, 过高浓度的氧对细胞反而具有损伤应激作用。除生理性低氧外, 机体经常会有病理性低氧的发生, 如心肌梗塞, 脑卒中等, 这时相应的组织细胞处于缺血缺氧的状态中, 尽管缺血的组织氧和营养都不足, 但缺氧可单独影响细胞的生理学特性。那么在低氧下, MSC 的存活、增殖、分化, 以及迁移能力有什么样的变化呢? 低氧对间充质干细胞凋亡和存活的影响干细胞移植研究是一大热点, 但移植到缺血的部位后不是所有细胞都可以存活。实验证