Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning.
Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning.
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DOI：
10.1038/cddis.2009.22
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发表时间：
2010
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
移植源自人类胚胎干细胞（hESC）的神经祖细胞为缺血性中风提供了潜在的治疗方法。然而，宿主环境中移植物存活率低阻碍了基于细胞的疗法的益处和应用。本研究测试了增强 hESC 耐受性的预处理策略，从而提高移植物存活率和 hESC 移植的治疗潜力。 UC06 hESCs经历长达30天的神经诱导和终末分化，成为神经谱系细胞，表现出广泛的神经突和轴突投射，产生突触和动作电位。为了诱导细胞保护表型，hESC衍生的神经球在0.1%氧气下培养12小时，解离并在21%氧气下铺板以进行终末分化。免疫细胞化学和电生理学证明“缺氧预处理”促进神经元分化。蛋白质印迹显示，在缺氧和随后的复氧过程中，氧敏感转录因子缺氧诱导因子 (HIF)-1α 和 HIF-2α 显着上调，同时在 HIF 靶标（包括促红细胞生成素、血管内皮生长因子和 Bcl-2 家族成员）内产生双相反应。这种细胞保护表型导致过氧化氢损伤或氧糖剥夺后总存活率和神经前体细胞存活率增加 50%。细胞保护维持至少 5 天，并且与神经保护蛋白的上调相对应。这些结果表明，低氧预处理可用于提高人类神经前体移植疗法的有效性。
Transplantation of neural progenitors derived from human embryonic stem cells (hESCs) provides a potential therapy for ischemic stroke. However, poor graft survival within the host environment has hampered the benefits and applications of cell-based therapies. The present investigation tested a preconditioning strategy to enhance hESC tolerance, thereby improving graft survival and the therapeutic potential of hESC transplantation. UC06 hESCs underwent neural induction and terminal differentiation for up to 30 days, becoming neural lineage cells, exhibiting extensive neurites and axonal projections, generating synapses and action potentials. To induce a cytoprotective phenotype, hESC-derived neurospheres were cultured at 0.1% oxygen for 12 h, dissociated and plated for terminal differentiation under 21% oxygen. Immunocytochemistry and electrophysiology demonstrated the ‘hypoxic preconditioning' promoted neuronal differentiation. Western blotting revealed significantly upregulated oxygen-sensitive transcription factors hypoxia-inducible factor (HIF)-1α and HIF-2α, while producing a biphasic response within HIF targets, including erythropoietin, vascular endothelial growth factor and Bcl-2 family members, during hypoxia and subsequent reoxygenation. This cytoprotective phenotype resulted in a 50% increase in both total and neural precursor cell survival after either hydrogen peroxide insult or oxygen–glucose deprivation. Cellular protection was maintained for at least 5 days and corresponded to upregulation of neuroprotective proteins. These results suggest that hypoxic preconditioning could be used to improve the effectiveness of human neural precursor transplantation therapies.
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影响因子：
3.4
作者：
Darsalia, Vladimer;Kallur, Therese;Kokaia, Zaal
通讯作者：
Kokaia, Zaal
DOI：
10.1016/s0034-5687(01)00306-1
发表时间：
2001-11-15
期刊：
RESPIRATION PHYSIOLOGY
影响因子：
--
作者：
Erecinska, M;Silver, IA
通讯作者：
Silver, IA
影响因子：
5.3
作者：
Chavez, Juan C.;Baranova, Oxana;Pichiule, Paola
通讯作者：
Pichiule, Paola
DOI：
10.1124/jpet.107.121392
发表时间：
2007-08-01
影响因子：
3.5
作者：
Keogh, Christine L.;Yu, Shan Ping;Wei, Ling
通讯作者：
Wei, Ling
影响因子：
4
作者：
Horie, Nobutaka;So, Kenji;Shinohara, Kazuyuki
通讯作者：
Shinohara, Kazuyuki