Abstract

Enzymatic biofuel cells (EBFCs) have excellent potential as components in bioelectronic devices, especially as active biointerfaces to regulate stem cell behavior for regenerative medicine applications. However, it remains unclear to what extent EBFC-generated electrical stimulation can regulate the functional behavior of human adipose-derived mesenchymal stem cells (hAD-MSCs) at the morphological and gene expression levels. Herein, we investigated the effect of EBFC-generated electrical stimulation on hAD-MSC cell morphology and gene expression using next-generation RNA sequencing. We tested three different electrical currents, 127 ± 9, 248 ± 15, and 598 ± 75 nA/cm2, in mesenchymal stem cells. We performed transcriptome profiling to analyze the impact of EBFC-derived electrical current on gene expression using next generation sequencing (NGS). We also observed changes in cytoskeleton arrangement and analyzed gene expression that depends on the electrical stimulation. The electrical stimulation of EBFC changes cell morphology through cytoskeleton re-arrangement. In particular, the results of whole transcriptome NGS showed that specific gene clusters were up- or down-regulated depending on the magnitude of applied electrical current of EBFC. In conclusion, this study demonstrates that EBFC-generated electrical stimulation can influence the morphological and gene expression properties of stem cells; such capabilities can be useful for regenerative medicine applications such as bioelectronic devices.

Highlights

  • Characterization of Enzymatic biofuel cells (EBFCs) Used for Cellular Studies

  • We investigated human mesenchymal stem cell behavior with electrical stimulation delivered by EBFCs

  • We investigated human mesenchymal stem cell behavior with electrical stimula delivered by EBFCs

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Summary

Introduction

Electrical stimulation plays an important role in regulating the function of mammalian cells and tissues, including neurons, muscle, and cardiomyocytes. A specific range of electrical stimulation conditions plays a biophysical role in wound healing and homeostasis by regulating stem cell behavior [9,10]. Direct current electrical stimulation has been used to treat Parkinson’s disease [20]. Implanted electrical devices, such as deep brain stimulators [8,9], often cause surgical complications and inflammation caused by inorganic materials. Direct implantation of inorganic fuel cells can be substituted by indirect therapy using electromagnetic systems, the systems are expensive and provide only localized stimulation [21]. There is broad interest in alternative device designs, especially ones that are compatible with a wearable format

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