Extremely low frequency electromagnetic fields promote mesenchymal stem cell migration by increasing intracellular Ca and activating the FAK/Rho GTPases signaling pathways in vitro.
Abstract
BACKGROUND: The 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. METHODS: We 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. RESULTS: All 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. CONCLUSIONS: EMF 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.
AI evidence extraction
Main findings
In human bone marrow-derived MSCs, exposure to 7.5, 15, 30, 50, or 70 Hz EMF at 1 mT promoted cell migration. The migration increase was intracellular calcium-dependent and involved FAK activation with increased talin and vinculin expression, and activation of RhoA, Rac1, and Cdc42 associated with increased cytoskeletal organization.
Outcomes measured
- MSC migration
- Intracellular calcium dependence (via verapamil)
- FAK activation and focal contact proteins (talin, vinculin)
- Rho GTPase activities (RhoA, Rac1, Cdc42)
- Actin cytoskeletal organization (F-actin)
View raw extracted JSON
{
"study_type": "in_vitro",
"exposure": {
"band": "ELF",
"source": "other",
"frequency_mhz": null,
"sar_wkg": null,
"duration": null
},
"population": "Human bone marrow-derived mesenchymal stem cells (MSCs)",
"sample_size": null,
"outcomes": [
"MSC migration",
"Intracellular calcium dependence (via verapamil)",
"FAK activation and focal contact proteins (talin, vinculin)",
"Rho GTPase activities (RhoA, Rac1, Cdc42)",
"Actin cytoskeletal organization (F-actin)"
],
"main_findings": "In human bone marrow-derived MSCs, exposure to 7.5, 15, 30, 50, or 70 Hz EMF at 1 mT promoted cell migration. The migration increase was intracellular calcium-dependent and involved FAK activation with increased talin and vinculin expression, and activation of RhoA, Rac1, and Cdc42 associated with increased cytoskeletal organization.",
"effect_direction": "benefit",
"limitations": [],
"evidence_strength": "low",
"confidence": 0.7800000000000000266453525910037569701671600341796875,
"peer_reviewed_likely": "yes",
"keywords": [
"extremely low frequency",
"ELF-EMF",
"mesenchymal stem cells",
"migration",
"intracellular calcium",
"FAK",
"Rho GTPases",
"RhoA",
"Rac1",
"Cdc42",
"talin",
"vinculin",
"F-actin",
"Helmholtz coils",
"verapamil",
"PF-573228"
],
"suggested_hubs": []
}
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