title: The effect of low-frequency electromagnetic field on human bone marrow stem/progenitor cell differentiation.
abstract: Human bone marrow stromal cells (hBMSCs, also known as bone marrow-derived mesenchymal stem cells) are a population of progenitor cells that contain a subset of skeletal stem cells (hSSCs), able to recreate cartilage, bone, stroma that supports hematopoiesis and marrow adipocytes. As such, they have become an important resource in developing strategies for regenerative medicine and tissue engineering due to their self-renewal and differentiation capabilities. The differentiation of SSCs/BMSCs is dependent on exposure to biophysical and biochemical stimuli that favor early and rapid activation of the in vivo tissue repair process. Exposure to exogenous stimuli such as an electromagnetic field (EMF) can promote differentiation of SSCs/BMSCs via ion dynamics and small signaling molecules. The plasma membrane is often considered to be the main target for EMF signals and most results point to an effect on the rate of ion or ligand binding due to a receptor site acting as a modulator of signaling cascades. Ion fluxes are closely involved in differentiation control as stem cells move and grow in specific directions to form tissues and organs. EMF affects numerous biological functions such as gene expression, cell fate, and cell differentiation, but will only induce these effects within a certain range of low frequencies as well as low amplitudes. EMF has been reported to be effective in the enhancement of osteogenesis and chondrogenesis of hSSCs/BMSCs with no documented negative effects. Studies show specific EMF frequencies enhance hSSC/BMSC adherence, proliferation, differentiation, and viability, all of which play a key role in the use of hSSCs/BMSCs for tissue engineering. While many EMF studies report significant enhancement of the differentiation process, results differ depending on the experimental and environmental conditions. Here we review how specific EMF parameters (frequency, intensity, and time of exposure) significantly regulate hSSC/BMSC differentiation in vitro. We discuss optimal conditions and parameters for effective hSSC/BMSC differentiation using EMF treatment in an in vivo setting, and how these can be translated to clinical trials.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, USA; Wake Forest Center for Integrative Medicine, Wake Forest School of Medicine, Medical Center Blvd., Winston-Salem, NC 27157, USA. Electronic address: chrross@wakehealth.edu.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Ross
authors.affiliation: Wake Forest Institute for Regenerative Medicine, USA.
authors.forename: Mevan
authors.initials: M
authors.lastname: Siriwardane
authors.affiliation: Wake Forest Institute for Regenerative Medicine, USA.
authors.forename: Graça
authors.initials: G
authors.lastname: Almeida-Porada
authors.affiliation: Wake Forest Institute for Regenerative Medicine, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Porada
authors.affiliation: Department of Physiology and Biophysics, SUNY Stony Brook, Stony Brook, NY 11794, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Brink
authors.affiliation: Wake Forest Institute for Regenerative Medicine, USA.
authors.forename: George J
authors.initials: GJ
authors.lastname: Christ
authors.affiliation: Wake Forest Institute for Regenerative Medicine, USA.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Harrison
mesh_terms: D002454:Cell Differentiation; D020219:Chondrogenesis; D004574:Electromagnetic Fields; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis; D057170:Translational Research, Biomedical