Department of Dermatology and Department of Ophthalmology, Institute for Regenerative Cures, UC Davis School of Medicine, Davis, CA 95817, USA.
Stem Cell Rev Rep. 2011 Nov;7(4):987-96. doi: 10.1007/s12015-011-9247-5.
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.
干细胞治疗的一个主要障碍是移植的干细胞与目标宿主组织的归巢和整合不良。人诱导多能干细胞（hiPS 细胞）被认为是胚胎干细胞（ES 细胞）的极好替代品，我们测试了利用小的生理电场（EF）引导 hiPS 细胞到达其靶标的可行性。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，它们则定向迁移。这很重要，因为 hiPS 细胞的治疗用途发生在 3D 环境中。EF 暴露不会改变 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 细胞在 EF 中的定向迁移（电趋性），发现 hiPS 细胞比 hES 细胞对 EF 更敏感和定向，而 hES 细胞则向阴极迁移。Rho-kinase（ROCK）抑制是一种有助于干细胞扩增和存活的方法，它显著增加了 hiPS 细胞在 EF 中的迁移性，但将其定向性降低了 70-80%。因此，我们的研究表明，生理 EF 是 hiPS 细胞在 2D 或 3D 环境中迁移的有效导向线索，并且这种迁移将以 ROCK 依赖性的方式发生。我们目前的发现可能会导致在体内应用 EF 来引导移植干细胞迁移的技术。
