br Electromagnetic field resonance and signal transduction T
Electromagnetic field resonance and signal transduction The application of EMF signals appears to be more than a new tool in biophysics and information medicine. It uses the basic science of physics, which drives the chemistry and the biology, to effect a biological change. Low-frequency EMF is biologically significant in that it is endogenous to cell regulation, and the remarkable effectiveness of EMF resonance treatments reflects a fundamental aspect of biological systems. Although cell signaling is regarded as a fundamental aspect of biology it is usually thought of as a molecular function — for example, the second messenger role of Ca. However the volumes of literature published in the past 40years make it impossible to ignore the underlying electromagnetic nature of cell signaling and signal transduction. Ion cyclotron resonance helps regulate biological information in ways that biochemical remedies and pharmaceuticals cannot (Foletti et al., 2012; Lisi et al., 2008). Experiments in resonance effects involve generating cell communication signals by using ELF-EMF which can trigger specific biological pathways. The resonant frequencies applied to human stem/progenitor bafilomycin a1 autophagy are able to generate modifications in well-defined cells and strongly affect differentiation processes (Foletti et al., 2012). ELF resonance fields stimulate embryonic stem cell differentiation and demonstrate the synergistic effects of a physical stimulus (EMF) with a biochemical stimulus (differentiation media). The effect of EMF on stem/progenitor cell differentiation depends on specific parameters such as waveform, duration, frequency and field strength, as well as the cell type (Tsai et al., 2009; Schwartz et al., 2008).
Translation from in vitro to in vivo and clinical use The differentiation of hBMSCs has been extensively studied using in vitro assays with culture-expanded hBMSCs. Results, however, have not always been reliable and fully reproducible because of the vast heterogeneity of in vitro culture conditions and the impact of these conditions on phenotype. hBMSCs are known to undergo phenotypic alternations during ex vivo manipulations, losing expression of some markers while acquiring new ones (Jones et al., 2002). hBMSC phenotype and capabilities vary between in vivo and in vitro settings because of the removal from their natural environment and the use of chemical and physical growth conditions that can alter their characteristics. In vitro data are dependent on culture conditions for differentiation and expansion of hBMSC populations and are unlikely to be extrapolated to the native cells. The idea of monitoring and controlling BMSC differentiation is a crucial regulatory and clinical requirement. hSSCs/BMSCs can be harvested from bone marrow aspirates then isolated, expanded, and characterized (Chim et al., 2008). These stem/progenitor cells for regenerative medical applications should ideally be cultured in large quantities (107–109), and have the ability to be differentiated along multiple cell lineages in a reproducible manner. hBMSCs can express an osteoblastic phenotype when treated with BMP2, which is used clinically to induce bone formation, although high doses are required. PEMF has been reported to promote osteogenesis in vivo, in part through direct action on osteogenic cells (Schwartz et al., 2008). In vivo tissue engineering studies have revealed that the absence of an abundant source of cells accelerating the healing process is a limiting factor in the ability to repair articular cartilage. During cartilage regeneration, proliferation and differentiation of new chondrocytes are required, and in humans, EMF stimulation has been used in order to increase the spontaneous regenerative capacity of bone and cartilage tissue post-op, with no apparent side-effects (Zhong et al., 2012). It is important to note that in vitro assays for osteogenesis, chondrogenesis and adipogenesis have been shown to be unreliable and unable to predict in vivo differentiation. While the cartilage pellet culture is the gold standard by which to assess chondrogenic potential, this assay is prone to misinterpretation based on alcian blue, rather than description of pellets in which chondrocytes can be seen in lacunae, surrounded by matrix that stains purple with toluidine blue (metachromasia). Due to this challenge, certain assay results have not been reproducible (Bianco et al., 2008, 2013). There is also the misconception that clonogenic, adherent fibroblastic cells from any non-skeletal tissue are equivalent to BMSCs.