Extremely low frequency electromagnetic fields promote mesenchymal stem cell migration by increasing intracellular Ca2+ and activating the FAK/Rho GTPases signaling pathways in vitro

Abstract

BackgroundThe ability of mesenchymal stem cells (MSCs) to migrate to the desired tissues or lesions is crucial for stem cell-based regenerative medicine and tissue engineering. Optimal therapeutics for promoting MSC migration are expected to become an effective means for tissue regeneration. Electromagnetic fields (EMF), as a noninvasive therapy, can cause a lot of biological changes in MSCs. However, whether EMF can promote MSC migration has not yet been reported.MethodsWe evaluated the effects of EMF on cell migration in human bone marrow-derived MSCs. With the use of Helmholtz coils and an EMF stimulator, 7.5, 15, 30, 50, and 70 Hz/1 mT EMF was generated. Additionally, we employed the l-type calcium channel blocker verapamil and the focal adhesion kinase (FAK) inhibitor PF-573228 to investigate the role of intracellular calcium content, cell adhesion proteins, and the Rho GTPase protein family (RhoA, Rac1, and Cdc42) in EMF-mediated MSC migration. Cell adhesion proteins (FAK, talin, and vinculin) were detected by Western blot analysis. The Rho GTPase protein family activities were assessed by G-LISA, and F-actin levels, which reflect actin cytoskeletal organization, were detected using immunofluorescence.ResultsAll the 7.5, 15, 30, 50, and 70 Hz/1 mT EMF promoted MSC migration. EMF increased MSC migration in an intracellular calcium-dependent manner. Notably, EMF-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased talin and vinculin expression. Moreover, RhoA, Rac1, and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction.ConclusionsEMF promoted MSC migration by increasing intracellular calcium and activating the FAK/Rho GTPase signaling pathways. This study provides insights into the mechanisms of MSC migration and will enable the rational design of targeted therapies to improve MSC engraftment.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0883-4) contains supplementary material, which is available to authorized users.

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“…Overexpression of KiSS-1 reduces the invasiveness of colorectal cancer cells by blocking the PI3K/AKT/NF-κB pathway and inhibiting the expression of MMP-9 protein [37]. Studies have shown that RhoA signaling and the PI3K/AKT pathway mediate cancer cell invasion [38,39], and the FAK-RhoA pathway may influence cancer cell motility [40,41]. According to our results, sinulariolide inhibited the FAK/PI3K/AKT/mTOR pathway and reduced the MMP-2/-9 and uPA protein expressions, preventing invasion and migration of AGS and NCI-N87 cells.…”

Increased intracellular Cl- concentration improves airway epithelial migration by activating the RhoA/ROCK Pathway

“…Among several possible control elements of cytophysical properties, the Rho family of GTPases and downstream signals appear to play the most prominent role in modulating the biochemical pathways of cell migration 21 - 23 . Although [Ca 2+ ] i is known to be a prominent regulator that can exert multiple effects on the structure and dynamics of the actin cytoskeleton 24 , 25 , whether [Cl - ] i is involved this response remains poorly defined.…”

Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration

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