Synergistic effect of a LPEMF and SPIONs on BMMSC proliferation, directional migration, and osteoblastogenesis.

Pulsed electromagnetic fields (PEMFs) represent a new type of physiotherapy that has been shown to be effective for improving bone fracture healing and treating osteoporosis. Targeted therapy with bone marrow mesenchymal stem cells (BMMSCs) has been the focus of several recent studies. The key to such therapy is the effective application of certain nanomaterials in BMMSCs so they achieve an ideal target concentration under the influence of a PEMF. In our present study, the effects of a PEMF on the process of osteoblastogenesis were systematically investigated using superparamagnetic iron oxide nanoparticle (SPION)-labeled BMMSCs. Rat BMMSCs labeled with SPIONs were exposed to a low-frequency pulsed electromagnetic field (LPEMF) of 50 Hz at 1.1 mT. Exposure to the LPEMF resulted in an enhanced proliferation of SPION-labeled BMMSCs when compared with a control group. Furthermore, observations made by transmission electron microscopy (TEM) revealed greater cell concentrations in the central zone with exposure to the LPEMF than in the peripheral zone without LPEMF stimulation, indicating that a LPEMF could induce the migration of SPION-labeled BMMSCs towards a magnetic field. Transwell experiments confirmed that combining SPIONs with a LPEMF could significantly promote the directional migration of BMMSCs. Von Kossa and ALP staining of LPEMF-exposed SPION-labeled cells was more intense, and those cells displayed higher levels of ALP activity than control cells. The SPION-labeled, LPEMF-exposed cells also showed increased levels of osteogenesis-related gene and protein expression (e.g., ALP, OCN, and RUNX2) in PCR and western blot studies. Taken together, our findings suggest that a combination of LPEMF and SPIONs exerts a synergistic effect on promoting the directional migration and osteogenic differentiation of BMMSCs, indicating that application of a LPEMF in conjunction with SPIONs may constitute a method for treating bone defects.