br Conclusion Human BMSCs are a promising cell

Conclusion Human BMSCs are a promising cell type for regenerative medicine and tissue-engineering applications. They have the capacity for self-renewal and exhibit multipotent differentiation potential through which they can produce lineages such as osteoblasts, chondrocytes, and adipocytes (Charbord et al., 2011). hBMSCs possess characteristic Ca waves that are involved in intracellular signaling, exhibiting both short and long periods — the longer periods also operate during transcellular signaling (Sun et al., 2007). To date, research has focused on exogenous chemical and biological factors without considering physiological factors such as EMF (see https://www.osha.gov/SLTC/elfradiation/healtheffects.html). Perhaps it is due to the lack of knowledge of the difference between ionizing and non-ionizing EMF. In particular, ionizing radiation has been shown to cause harmful effects by breaking the bafilomycin a1 autophagy bonds that hold molecules like DNA together (Buonanno et al., 2011; Mobbs et al., 2011). EMF capable of generating ionizing fields includes current produced by power lines, electrical wiring, and high-energy electrical equipment. The energy in non-ionizing radiation, however, is not strong enough to break ion bonds in atoms and molecules (Ng, 2003; Tenforde and Kaune, 1987). Another issue in using EMF for differentiation of hBMSCs concerns the fact that investigators rarely discuss why they selected specific parameters for activating cell differentiation in their studies, leaving the reader to assume that their selections were random. In order to truly understand the mechanism of action of EMF on any cell type and its potential utility in developing novel therapies, it is imperative that parameters such as frequency, intensity, and time of exposure be optimized into a single, identified system where the experimental and environmental conditions are fixed, thereby permitting replication and optimization of a treatment shown to have regenerative effects. While much of the EMF research has focused on the differentiation of hBMSCs to bone, it appears that the same 15Hz frequency stimulates hBMSCs to initiate chondrogenesis, however the field strength is more intense (5mT versus <2mT) (Mayer-Wagner et al., 2011). Since cartilage formed by hBMSCs typically undergoes hypertrophy or directly forms bone (Scotti et al., 2010; Serafini et al., 2014), it is not surprising that these two tissues would respond to the same frequency; however it is interesting to note that the field strength is more than double for chondrogenesis than that of osteogenesis. While it remains difficult to alter the expression of genes to rebuild damaged tissues in humans, especially when considering the use of controversial treatments such as stem cell and gene therapies, a systems-based view of development and regeneration may provide suitable therapeutic alternatives. Complex interactions of multiple genetic substances give rise to physical cues, including mechanical and electrical signals that are relatively easier to control and implement in order to guide repair and regeneration. Treatment using EMF could be an auxiliary approach to enhancing cellular activities for tissue regeneration by stimulating cells with both EMF and the proper chemical signals (differentiation media and growth factors) to promote cellular responses synergistically. Additionally, this inherently noninvasive and noncontact treatment method is easily applied to cells for tissue regeneration using three-dimensional scaffolds (Kim et al., 2011; Konrad et al., 1996; Liu et al., 2012; Trock, 2000; Yun JH et al., 2012). Exposure of the EMF to cells on scaffolds with specific conditions has been reported to accelerate tissue formation (Saino et al., 2011).
Introduction There are several challenges to producing cell-based therapies of the quality, safety and scale needed for clinical use. The use of somatic stem cells offers the advantage of avoiding the issue of tumorigenicity and costly reprogramming linked to the use of ES and iPS (Ben-David and Benvenisty, 2011; Bianco et al., 2013), as well as offering the possibility of using minimally manipulated autologous stem cells and thereby preventing any risk of rejection or Graft-versus-Host-Disease seen with the use of allogeneic tissues and cells. Important factors to be considered in the development of cell transplantation therapies are availability and differentiation potential of the stem cell type selected, and the use of allogeneic versus autologous stem cells.