Electrically Guiding Migration of Human Induced Pluripotent Stem Cells

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s12015-011-9247-5) contains supplementary material, which is available to authorized users.

Directed migration of human bone marrow mesenchymal stem cells in a physiological direct current electric field

“…Here, adult human bone marrow-derived MSCs showed strong anodal electrotaxis in physiological EFs, and this migration response increased with increasing EF strength between 25-300 mV/mm. Human induced pluripotent stem cell (hiPS) also show anodal electrotaxis in physiological EFs (Zhang et al, 2011). However, mouse adipose-derived stromal cells (mASC) migrated towards the cathode in response to EFs (Hammerick et al, 2010).…”

“…There are many advantages to using low voltages for EF stimulation. The most important ones for developing a practical technique of EF application is that this will signifi cantly prevent electro-chemical product generation (from electrodes), the generation of heat, and effects on other cell types in 3D tissues Zhang et al, 2011). This will also allow more prolonged application in clinical practice.…”

Electrotaxis of oral squamous cell carcinoma cells in a multiple-electric-field chip with uniform flow field

“…From early research, electrotaxis has been known to play a profound role in embryonic development, neurogenesis, and wound healing. 1,2 Many different cell types and organisms show electrotactic response to dcEF, including neural stem cell, 3 induced pluripotent stem cells, 4 mesenchymal stem cells, 5,6 fibroblasts, [7][8][9] keratinocytes, 10,11 neurons, 2 and C. elegans. 12,13 The physiological dcEF with strength of tens to hundreds of mV per mm (mVÁmm À1 ) originates from the difference in transepithelial potential (TEP), which is supposedly formed by the differential distribution of ion channels on polarized epithelial cells.…”

Recent Developments in Electrotaxis Assays

“…Zhang et al reported the use of the 3D Matrigel for studying electrotaxis of human induced pluripotent stem (hiPS) cells. 14 The cells were mixed with Matrigel followed by transference to the electrotactic chamber. The study showed that dcEF can stimulate and direct hiPS cell migration in 3D.…”