The roles of apoptotic pathways in the low recovery rate after cryopreservation of dissociated human embryonic stem cells.

The roles of apoptotic pathways in the low recovery rate after cryopreservation of dissociated human embryonic stem cells.
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DOI:
10.1002/btpr.368
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发表时间:
2010-05
影响因子:
2.9
通讯作者:
Cui, Zhanfeng
Cui, Zhanfeng
中科院分区:
工程技术4区
文献类型:
--
作者:
Xu, Xia;Cowley, Sally;Flaim, Christopher J.;James, William;Seymour, Leonard;Cui, Zhanfeng

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人类胚胎干细胞(human embryonic stem cells,hES)具有巨大的临床应用潜力。然而,一个主要的挑战是在冷冻保存后实现高细胞回收率。了解常规的冷冻保存方案如何不能保护细胞是为hES细胞系和细胞库开发有效和成功的冷冻保存方法的先决条件。我们研究了冻存刺激如何导致细胞凋亡,这导致冻存后细胞恢复率低。超低温保存后,细胞内活性氧(ROS)水平显著升高,F-肌动蛋白含量和分布发生变化,caspase-8和caspase-9被激活。p53也被激活并移位到细胞核中。在冷冻保存过程中,细胞凋亡是通过激活caspase-8通过外源途径和caspase-9通过内源途径诱导的。然而,外源性通路究竟是如何被激活的仍不清楚,值得进一步研究。© 2010美国化学工程师学会生物技术。程序:2010
Human embryonic stem (hES) cells have enormous potential for clinical applications. However, one major challenge is to achieve high cell recovery rate after cryopreservation. Understanding how the conventional cryopreservation protocol fails to protect the cells is a prerequisite for developing efficient and successful cryopreservation methods for hES cell lines and banks. We investigated how the stimuli from cryopreservation result in apoptosis, which causes the low cell recovery rate after cryopreservation. The level of reactive oxygen species (ROS) is significantly increased, F-actin content and distribution is altered, and caspase-8 and caspase-9 are activated after cryopreservation. p53 is also activated and translocated into nucleus. During cryopreservation apoptosis is induced by activation of both caspase-8 through the extrinsic pathway and caspase-9 through the intrinsic pathway. However, exactly how the extrinsic pathway is activated is still unclear and deserves further investigation. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010
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