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Extremely Low-frequency Electromagnetic Fields Induce Neural Differentiation In Bone Marrow Derived Mesenchymal Stem Cells

Hyun-Jung Kim, Jessica Jung, Jee-Hye Park, Jin-Hee Kim, Kyung-Nam Ko, Chan-Wha Kim

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Extremely low-frequency electromagnetic fields (ELF-EMF) affect numerous biological functions such as gene expression, cell fate determination and even cell differentiation. To investigate the correlation between ELF-EMF exposure and differentiation, bone marrow derived mesenchymal stem cells (BM-MSCs) were subjected to a 50-Hz electromagnetic field during in vitro expansion. The influence of ELF-EMF on BM-MSCs was analysed by a range of different analytical methods to understand its role in the enhancement of neural differentiation. ELF-EMF exposure significantly decreased the rate of proliferation, which in turn caused an increase in neuronal differentiation. The ELF-EMF-treated cells showed increased levels of neuronal differentiation marker (MAP2), while early neuronal marker (Nestin) was down-regulated. In addition, eight differentially expressed proteins were detected in two-dimensional electrophoresis maps, and were identified using ESI-Q-TOF LC/MS/MS. Among them, ferritin light chain, thioredoxin-dependent peroxide reductase, and tubulin β-6 chain were up-regulated in the ELF-EMF-stimulated group. Ferritin and thioredoxin-dependent peroxide reductase are involved in a wide variety of functions, including Ca2+ regulation, which is a critical component of neurodegeneration. We also observed that the intracellular Ca2+ content was significantly elevated after ELF-EMF exposure, which strengthens the modulatory role of ferritin and thioredoxin-dependent peroxide reductase, during differentiation. Notably, western blot analysis indicated significantly increased expression of the ferritin light chain in the ELF-EMF-stimulated group (0.60 vs. 1.08; P < 0.01). These proteins may help understand the effect of ELF-EMF stimulation on BM-MSCs during neural differentiation and its potential use as a clinically therapeutic option for treating neurodegenerative diseases.