Electrical Stimulation Mobilized and Guided Migration of hNSCs in Rat Brain
(A) hNSCs transplanted into the middle part of rostral migration stream (RMS) had a default migration toward the olfactory bulb (OB). EGFP signals are evidently present on the OB side (A′), No EGFP signal was detectable on the lateral ventricle (LV) side (A″).
(B) Electrical stimulation (positive at OB and negative at LV side) induced significant amount of hNSCs to migrate to the LV side (B″) against co-existing guidance cues which normally guide cells to the OB side in the RMS. Larger number of hNSCs kept migration to the OB (B′). Electrodes were implanted and electrical stimulation was applied for 10 hr after 24 hr of EGFP-hNSC transplantation.
(C and D) Adjacent sections of the brain confirmed migration of hNSCs to the LV side.
(E) Sham stimulation, whereby stimulation electrodes were inserted without delivery of currents, showed no cell migration to the LV side (E″).
(F and G) Semi-quantification confirmed mobilizing and guidance effects of electrical stimulation. Electrical stimulation toward the SVZ guided a significant amount of hNSCs to the LV side, which was not seen in control groups. The maximum direct migration distance toward LV was 2.4 mm.
Means ± SEM from three independent experiments. ∗∗p < 0.01 versus electrode implant with no EF. Red arrowhead, cell transplant site; white arrow, injection needle path; red arrow, electrode insertion path. In (A) to (E″), DAPI is blue, EGFP green, and human SOX-2 red. Scale bars, 1 mm (A, B, and E), 500 μm (C), and 100 μm (A′, A″, B′, B″, D, E′, and E″).