Electrically guiding migration of human induced pluripotent stem cells.

Electrically guiding migration of human induced pluripotent stem cells.
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DOI:
10.1007/s12015-011-9247-5
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发表时间:
2011-11
影响因子:
4.8
通讯作者:
Zhao, Min
Zhao, Min
中科院分区:
医学3区
文献类型:
--
作者:
Zhang, Jiaping;Calafiore, Marco;Zeng, Qunli;Zhang, Xiuzhen;Huang, Yuesheng;Li, Ronald A.;Deng, Wenbin;Zhao, Min

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干细胞治疗的一个主要障碍是移植的干细胞与靶宿主组织的归巢和整合不良。人类诱导多能干细胞(hiPS)被认为是胚胎干细胞(ES)的极好替代品,我们测试了使用小的生理电场(EFs)引导hiPS细胞到达目标的可行性。施加的EF刺激并引导培养的hiPS细胞向阳极迁移,刺激阈值<30 mV/mm;在三维(3D)培养中,hiPS细胞保持静止,而在施加的EF中,它们定向迁移。这是重要的,因为hiPS细胞的治疗用途发生在3D环境中。EF暴露不改变hiPS细胞中多能性标志物SSEA-4和Oct-4的表达。我们比较了hiPS细胞和hES细胞的EF定向迁移(趋电性),发现hiPS细胞在EF中表现出比hES细胞更高的敏感性和定向性,而hES细胞向阴极迁移。Rho激酶(ROCK)抑制,一种帮助干细胞扩增和存活的方法,显著增加了运动性,但将EF中iPS细胞的方向性降低了70- 80%。因此,我们的研究表明,生理EF是一个有效的指导线索,无论是在2D或3D环境中的hiPS细胞的迁移,将发生在一个ROCK依赖的方式。我们目前的发现可能会导致在体内应用EFs指导移植干细胞迁移的技术。本文的在线版本(doi:10.1007/s12015-011-9247-5)包含补充材料,可供授权用户使用。
A major road-block in stem cell therapy is the poor homing and integration of transplanted stem cells with the targeted host tissue. Human induced pluripotent stem (hiPS) cells are considered an excellent alternative to embryonic stem (ES) cells and we tested the feasibility of using small, physiological electric fields (EFs) to guide hiPS cells to their target. Applied EFs stimulated and guided migration of cultured hiPS cells toward the anode, with a stimulation threshold of <30 mV/mm; in three-dimensional (3D) culture hiPS cells remained stationary, whereas in an applied EF they migrated directionally. This is of significance as the therapeutic use of hiPS cells occurs in a 3D environment. EF exposure did not alter expression of the pluripotency markers SSEA-4 and Oct-4 in hiPS cells. We compared EF-directed migration (galvanotaxis) of hiPS cells and hES cells and found that hiPS cells showed greater sensitivity and directedness than those of hES cells in an EF, while hES cells migrated toward cathode. Rho-kinase (ROCK) inhibition, a method to aid expansion and survival of stem cells, significantly increased the motility, but reduced directionality of iPS cells in an EF by 70–80%. Thus, our study has revealed that physiological EF is an effective guidance cue for the migration of hiPS cells in either 2D or 3D environments and that will occur in a ROCK-dependent manner. Our current finding may lead to techniques for applying EFs in vivo to guide migration of transplanted stem cells. The online version of this article (doi:10.1007/s12015-011-9247-5) contains supplementary material, which is available to authorized users.
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