Abstract

Extremely low-frequency pulsed electromagnetic field (ELF-PEMF) devices have been used in the clinic for the treatment of bone disorders over the past 30 years. However, the underlying mechanism of which ELF-PEMFs exert an effect on tissues at a cellular level is not well understood. Hence, in this study, we explored the potential of different ELF-PEMF signals in modulating human adipose-derived mesenchymal stromal cells' (hAMSC) osteogenic capability. The cell proliferation rate was assessed using carboxyfluorescein succinimidyl ester (CFSE) method. The osteogenesis potential of cells was determined by alkaline phosphatase (ALP) activity, Alizarin-Red S staining, and RT-qPCR. Finally, the intracellular signaling pathway of a selected ELF-PEMF signal was examined using the PathScan Intracellular Signaling Array. Among the tested ELF-PEMF signals, program 20 (26 Hz) showed activation of the Akt and MAPK/ERK signaling cascade and significant upregulations of collagen I, alkaline phosphatase, and osteocalcin when compared to nonstimulated cells. This study demonstrates the potential of certain ELF-PEMF signal parameters to induce osteogenic differentiation of hAMSC and provides important clues in terms of the molecular mechanisms for the stimulation of osteogenic effects by ELF-PEMF on hAMSC.

Highlights

  • Clinical intervention of large bone defects is limited

  • In this study, we explored the potential of different ELF-PEMF signals in modulating human adipose-derived mesenchymal stromal cells’ osteogenic capability

  • This study demonstrates the potential of certain ELF-PEMF signal parameters to induce osteogenic differentiation of human adipose-derived mesenchymal stromal cells’ (hAMSC) and provides important clues in terms of the molecular mechanisms for the stimulation of osteogenic effects by ELF-PEMF on hAMSC

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Summary

Introduction

Autografts (transplantation of patient’s own tissue) remain the gold standard for treating large bone defects. Cell therapy has been proven to be a viable strategy that can aid the process of bone regeneration [1]. The efficacy of AMSC therapy depends upon how effectively transplanted AMSC can be targeted persistently to the diseased area and how functional these cells are in terms of the regeneration process. One crucial phase of bone regeneration is the proliferation and differentiation of precursor cells (i.e., MSC) into osteoblasts (bone-forming cells) that would build up the mineralized bone matrix. There have been tremendous efforts in the development of noninvasive strategies, which could complement cell therapy by stimulating proliferation and guiding differentiation of MSC within the injured sites

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