Directed migration of human bone marrow mesenchymal stem cells in a physiological direct current electric field
1 Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK
* These authors contributed equally as corresponding authors
Abstract
At sites of bone fracture, naturally-occurring electric fields (EFs) exist during healing and may guide cell migration. In this study, we investigated whether EFs could direct the migration of bone marrow mesenchymal stem cells (BM-MSCs), which are known to be key players in bone formation. Human BM-MSCs were cultured in direct current EFs of 10 to 600 mV/mm. Using time-lapse microscopy, we demonstrated that an EF directed migration of BM-MSCs mainly to the anode. Directional migration occurred at a low threshold and with a physiological EF of ~25 mV/mm. Increasing the EF enhanced the MSC migratory response. The migration speed peaked at 300 mV/mm, at a rate of 42 ±1 µm/h, around double the control (no EF) migration rate. MSCs showed sustained response to prolonged EF applicationin vitroup to at least 8 h. The electrotaxis of MSCs with either early (P3-P5) or late (P7-P10) passage was also investigated. Migration was passage-dependent with higher passage number showing reduced directed migration, within the range of passages examined. An EF of 200 mV/mm for 2 h did not affect cell senescence, phenotype, or osteogenic potential of MSCs, regardless of passage number within the range tested (P3-P10). Our findings indicate that EFs are a powerful cue in directing migration of human MSCsin vitro. An applied EF may be useful to control or enhance migration of MSCs during bone healing.
Keyword
- Adult human bone marrow; mesenchymal stem cells; cell migration; tissue regeneration; direct-current electric fields; osteogenesis
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