Human embryonic stem cells: caught between a ROCK inhibitor and a hard place
Human embryonic stem cells: caught between a ROCK inhibitor and a hard place
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DOI：
10.1002/bies.200800157
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发表时间：
2009-03-01
期刊：
影响因子：
4
通讯作者：
Rancourt, Derrick E.
中科院分区：
文献类型：
--
作者：
Krawetz, Roman J.;Li, Xiangyun;Rancourt, Derrick E.
自其衍生以来，人类胚胎干细胞（hES）已被用于各种应用，包括发育生物学、病理学、化学生物学、基因组学和蛋白质组学。然而，它们最重要的潜在应用是生成细胞和组织，可用于基于细胞的治疗。hES细胞培养的主要缺点之一是它们对解离特别敏感，而解离是传代、扩增、冷冻保存和其他应用所必需的。最近，人们发现一种Rho激酶抑制剂（ROCKi; Y-27632）可以提高游离的单个hES细胞的存活率。这一突破使得人类胚胎干细胞培养的新方法得以开发，并有望将人类胚胎干细胞数量增加到临床应用领域。在我们的研究中，ROCKi显著提高了hES细胞的低温保存效率，我们观察到ROCKi处理并没有降低hES细胞的凋亡易感性。相反，我们假设ROCKi治疗使单个he细胞对其环境脱敏，从而降低了单个细胞发生突变的几率。
Since their derivation, human embryonic stem (hES) cells have been used for a variety of applications including developmental biology, pathology, chemical biology, genomics, and proteomics. However, their most important potential application is the generation of cells and tissues, which can be used for cell-based therapies. One of the main drawbacks of hES cell culture is that they are particularly sensitive to dissociation, which is required for passaging, expansion, cryopreservation, and other applications. Recently, it has been discovered that an inhibitor of Rho kinase (ROCKi; Y-27632) increases the survival rate of dissociated, single hES cells. This break-through has allowed new methods in hES cell culture to be developed, with the promise of increasing hES cell numbers into the realm of clinical relevance. In our studies demonstrating that ROCKi dramatically increases hES cell cryopreservation efficiency, we have observed that ROCKi treatment does not decrease hES cell's susceptibility to apoptosis. Rather, we hypothesize that ROCKi treatment desensitizes single hES cells to their environment reducing the odds that individual cells will undergo anoikis.