Stem Cells International

Review Article

Electromagnetic Fields for the Regulation of Neural Stem Cells

Table 1

Current studies of electromagnetic fields and transcranial magnetic stimulation.


Category	Model	Method of stimulation	Field intensity	Stimulation pattern	Stimulation duration	Post stim assessment	Region assessed	Main effect of TMS	Potential mechanism	Reference

In vitro	Embryonic neural stem cells (eNSCs) from embryonic day 13.5 (E13.5) BALB/c mice	sXc-ELF exposure system (IT’IS Foundation, Zurich, Switzerland)	1 mT	Exposed to ELF-EMF (50 Hz, 1 mT) for 1, 2, and 3 days with 4 hours per day	1/2/3 days	Same day	eNSCs in vitro	The neuronal differentiation ↑ Neurite outgrowth ↑	The expression of TRPC1 and proneural genes (NeuroD and Ngn1) ↑	Ma et al. (2016) [95]
	Embryonic neural stem cells (eNSCs) from embryonic day 13.5 (E13.5) BALB/c mice	sXc-ELF exposure system (IT’IS Foundation, Zurich, Switzerland)	0.5 mT, 1 mT, and 2 mT	At a frequency of 50 Hz sinusoidal waves with magnetic intensities of 0.5 mT, 1 mT, and 2 mT for 3 days or with a magnetic intensity of 2 mT for 1 day, 2 days, and 3 days, with an intermittent cycle of 5 min on/10 min	1/2/3 days	Same day	eNSCs in vitro	Intermittent exposure to ELF-EMF no change in proliferation of eNSCs and percentages of Tuj1-positive cells and GFAP	Sox2↓ Math1, Math3, Ngn1 Tuj1 mRNA levels ↑	Ma et al. (2014) [96]
	NSCs from the hippocampus of neonatal 3-day-old SD rats	rTMS 90 mm figure-of-eight coil (Yirui De, CCY-I, Wuhan, China)	50% of the device’s maximum power (peak value 3.5 T)	200/400/600/800/1000 pulses per day, 10 s trains with 10 Hz frequency	3 days	Same day	NSCs in vitro	NSC proliferation in vitro in a dose-dependent manner ↑	miR-106b expression ↑ miR-106b/p21/cdks/cyclin pathway	Liu et al. (2015) [65]
	Neonatal rat neural stem cells	HMF-S20-type pulsed magnetic field device (manufactured by High Magnetic Center of Huazhong University of Science and Technology)	0.5–10 T	0.1 Hz, 0.5–10 Tesla (T) [8 groups of B–I, resp.]	5 stimuli of high-intensity pulsed electromagnetic field (HIPEMF)	24th h, 48th h, 72nd h, and 7th day	NSCs in vitro	6.0–10.0 T peak intensity led to poor growth of rat NSCs in vitro, and in the condition of 0.5–4.0 T peak intensity, HIPEMF stimulated the proliferation of rat NSCs	___	Meng et al. (2009) [52]
	NSCs from postnatal day 0 (P0) CD-1 mice	Solenoid generating alternating EFs	1 mT	50 Hz continuously	Up to 12 days	Same day	NSCs in vitro	Neurogenesis ↑	Cav1 channel activity ↑ intracellular Ca2þ signaling ↑	Piacentini et al. (2008) [73]
	Normal, healthy mice	rTMS (model 9000 MS, Neurosoft, Ivanovo, Russia) 100 mm circular coil	Maximum output intensity of the device	1 Hz and 30 Hz	1 Hz: received 150 pulses/day (5 second train, 10 second pause) in 450 seconds and 30 Hz group received 150 pulses/day (1 second train, 5 second pause) in 30 seconds. 7 or 14 consecutive days	7 days or 14 days	NSCs from subventricular zone	NS/PC proliferation and neuronal differentiation ↑	BDNF; activation of different neurotransmitter system	Abbasnia et al. (2015) [16]

In vivo	NSCs from the hippocampi of newborn C57bl/6 mice	Solenoid generating alternating EFs characterized by a sinusoidal waveform with amplitudes of 5–1000 μT and frequencies of 1–100 Hz	1 mT	50 Hz; 3.5 h/day	12 days (12 D × 3.5 h)	One month	Hippocampal dentate gyrus	Proliferation and neuronal differentiation of NSCs ↑	pCREB signaling pathway epigenetic modulation	Leone et al. (2014) [68]
	Adult male SD rats model of depression in chronic unpredictable stress	rTMS round coil (inner diameter, 2.5 cm; outer diameter, 5 cm; custom-made YIRD, China)	1.26 T	15 Hz, 15 s trains, 900 pulses daily	7 days	1 day	Hippocampal dentate gyrus	NSPC proliferation ↑	BDNF expression; BDNF/ERK signaling pathway ↑	Chen et al. (2015) [57]
	Ischemic injury in rats	rTMS round prototype coil 6 cm in diameter with 3.5 T peak magnetic welds (YRD-CCI, Wuhan, China)	Stimulation intensity was set at 120% of the average resting motor threshold (RMT), namely, 26% of the maximum output of the stimulator	Stimulation for 3 s followed by rest for 50 s, which was repeated ten times (300 pulses per day) at the rate of 10 Hz	7 days	12 h	The ischemic cortex subventricular zone (SVZ)	Adult NSC proliferation ↑	miR-25 expression ↑ miR-25/p57/cdks/cyclins pathway	Guo et al. (2014) [55]
	Ischemic injury in male Wistar rats	rTMS figure-of-eight coil (CCY-II, Wuhan Yiruide Medical Equipment, Wuhan, China)	20 Hz group: 120% RMT (24% of the maximum stimulator output) iTBS80% RMT (16% of the maximum stimulator output)	40 trains at 20 Hz for 1 s 15 s interval 20 trains with 600 pulses	10 days	2 days	Ipsilateral SVZ peri-infarct striatum	Improvements of functional recovery ↑ Volume of the infarct area ↓ Migration, differentiation, and proliferation ↑	BDNF/TrkB signaling pathway; ↑ expression levels of BDNF ↑	Luo et al. (2017) [51]
	Normal, healthy mice	Deep brain magnetic stimulation via two coils placed either side of the cage	10 mT peak	Varying pulsed magnetic fields	4 or 7 days	1 day	Dentate gyrus	NSPC proliferation Neurogenesis ↑	c-fos gene; ↑ expression level of fgf1b ↑; stimulate neural activity in certain brain regions by modulating the balance between excitatory and inhibitory neurons	Zhang et al. (2014) [97]
	Nigrostriatal lesion and chromaffin cell transplant in rats	Oscillatory magnetic field via two 7 cm Hemholtz coils positioned dorsal and ventral to the head	0.7 mT	60 Hz, 2 h morning and afternoon	60 Hz, 2 h morning and afternoon	Same day	SVZ	NSPC proliferation ↑	—	Arias-Carrion et al. (2004) [50]
	Normal, healthy rats	rTMS figure-of-eight coil	70% maximum power	25 Hz, 4 × 10 s trains daily	14 days	1 day	Dentate gyrus	NSPC proliferation neurogenesis ↑	—	Ueyama et al. (2011) [53]
	Normal, healthy C57 mice	Solenoid generating alternating EFs	1 mT	1 to 7 h/day for 7 days	7 days	Same day	Dentate gyrus (DG)	NSC proliferation ↑	Expression of Mash1, Hes1 ↑, and NeuroD2 mRNAs; ↑ Ca²⁺ influx ↑	Cuccurazzu et al. (2010) [49]