Preconditioning with repetitive electromagnetic stimulation enhances activity of bone marrow mesenchymal stem cells from elderly patients through Erk1/2 via nitric oxide

Use of bone marrow aspirate (BMA) is a clinically advantageous cell therapeutic that bypasses the need for elaborate ex vivo cell culturing. However, a low level of bone marrowmesenchymal stem cells (BMMSCs) in the BMA and weak survival rate of these cells posttransplantation entails an insufficient efficacy in vivo. Moreover, stem cell activity in BMA is impaired by age or background diseases. Thus, in order to enrich the BMMSC pool and improve cell survival, novel cell preconditioning technologies are required. In this study, it has been revealed that the pretreatment of repetitive electromagnetic stimulation (rEMS) is capable of enhancing fibroblastic colonyforming units and cell proliferation in the BMMSCs, possibly via transient nitric oxide production and extracellular signal regulated kinase 1/2 activation. Notably, this effect was more apparent in stem cells isolated from older patients than from young patients. Furthermore, the rEMSpretreated cells showed ~53% higher cell survival, compared with the untreated cells, after cell transplantation in mice with no signs of tumorigenesis. Collectively, transient rEMS preconditioning could be utilized to enhance the activity of stem cells and thus, application of rEMS preconditioning to stem cells isolated from older patients is expected to improve the therapeutic effect of stem cells.