Abstract
The medical applications of electrical biostimulation and silver ions have been evaluated in laboratory experiments and clinical studies for more than two decades. Their effects on preventing infection and promoting wound healing have been described. However, little is known about the role of electrical biostimulation and/or silver ion on changes in cellular transcriptome dynamics. To our knowledge, few studies have been conducted to investigate the potential of electrical biostimulation and silver ions in cell reprogramming. Besides, it is essential to assess any possible adverse effects or potential benefits of the silver ions on mammalian cells to address its safety concerns and to improve silver medical products. In this study, we investigated transcriptomic changes in porcine fibroblast cells in response to electrical biostimulation in the presence of silver ions. Exposed cells presented distinct morphological changes after treatment, which was mainly due to the exposure of silver ions rather than the electrical current itself. Gene expression analyses suggested that electrical biostimulation and silver ions did not increase the expression of pluripotency genes. Interestingly, a set of genes related to cellular metabolic processes were differentially expressed after cells were exposed to electrically generated silver ions for 21 hours. We found that 2.00 mg/L of electrically generated silver ion caused an increase of ATP generation and an increase of the total pool of NAD+ and NADH, while ROS production did not change. Aside from toxic effects, the results reported herein demonstrate the alternative effects of silver ions on mammalian cells, especially an oxidative phosphorylation burst. To our knowledge, this response of mammalian cells to silver ions has not been described previously. Although the function of this burst is not understood, it may lead to alterations in cellular activities such as metabolic remodeling and cell reprogramming, and/or serve an as-yet unknown function in neutralization or detoxification of the silver ions within the cells.
Highlights
Bioelectric properties or signals play a key role in many biological processes and cell behaviors, such as proliferation, mitosis, apoptosis, migration, orientation, differentiation, and de-differentiation [1]
The highest concentration of silver ions in the medium was detected when 580 nA of direct current was applied. As these data proved, it is important to note that the term “electrical biostimulation” we described in this study should include at least two factors without repeated explanation, which are the electromagnetic field and the electrically generated silver ions
Compared with the findings reported by Stoehr et al, where the epithelial cells rounded up and detached from the plastic support after exposed to silver wires and microparticles for 24 hours [38], our fibroblast cells showed similar morphological changes after exposure to electrical biostimulation and silver ions in the present study
Summary
Bioelectric properties or signals play a key role in many biological processes and cell behaviors, such as proliferation, mitosis, apoptosis, migration, orientation, differentiation, and de-differentiation [1]. The electrical biostimulation is one of the simplest methods of electromagnetic biostimulation used to investigate how cells respond when exposed to electrical currents of different amplitudes and frequencies. This method has been applied to in vitro studies, animal experiments, and clinical trials for wound healing and bone regeneration [2,3,4]. The concept of cell transformation into a relatively undifferentiated state led us to consider the possibility that electrical field stimulation might have the capability to directly induce de-differentiation or cellular reprogramming
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