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.

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“…In the sinusoidal electric field the value of the current in the body increases with the magnitude of the frequency [4]. ELF magnetic field has biological effects such as, inducing cell metabolism [3], altering chemical or enzyme processes (Agustrina, 2013: 405-412), and altering membrane surface properties [13]. The ability of the biological effects of the magnetic field to affect the permeability of the ion channels in the membrane can give the effect of ion transport into the cell and give changes to the organism [6].…”

The Stem Cell Division Theory of Cancer

“…It is also known that HSCs migrate during embryonic development and early childhood; the migration of HSCs allows different sites to participate in hematopoiesis at different moments in life [184,185]. Importantly, numerous investigations have shown that ELF-EMFs can stimulate the division of stem cells and promote tissue regeneration [34,[186][187][188][189][190][191][192]. In addition, cell migration is regulated by physiological electric currents [123,[193][194][195], and ELF-EMFs are known to induce electric currents that can alter cell migration [34,88,191,192,[196][197][198].…”

A Plausible Biological Mechanism by which Extremely Low-Frequency Electromagnetic Fields Increase the Risk of Childhood Leukemia

“…Numerous investigations have shown that ELF-EMFs can stimulate the division of stem cells [37][38][39][40][41]. It is well established that exposure to ELF-EMFs results in induction of electric fields and associated currents in tissues, an effect that has been used to promote tissue regeneration [1,42,43].…”

“…This effect has been observed with relatively weak magnetic fields (µT and mT) [1,44]. Since the division of stem cells is crucial for tissue regeneration, it is not surprising that ELF-EMFs can stimulate the division of stem cells of a variety of tissues [37][38][39][40][41].…”