Effect of Electrical and Electromechanical Stimulation on PC12 Cell Proliferation and Axon Outgrowth.

Kailei Xu,Jin Qian,Jun Yin,Xiaokeng Li,Xixia Liu,Jie Sun,Peng Wei

doi:10.3389/fbioe.2021.757906

Abstract

Peripheral nerve injuries have become a common clinical disease with poor prognosis and complicated treatments. The development of tissue engineering pointed a promising direction to produce nerve conduits for nerve regeneration. Electrical and mechanical stimulations have been incorporated with tissue engineering, since such external stimulations could promote nerve cell proliferation, migration and differentiation. However, the combination of electrical and mechanical stimulations (electromechanical stimulation) and its effects on neuron proliferation and axon outgrowth have been rarely investigated. Herein, silver nanowires (AgNWs) embedded polydimethylsiloxane (PDMS) electrodes were developed to study the effects of electromechanical stimulation on rat pheochromocytoma cells (PC12 cells) behaviors. AgNWs/PDMS electrodes demonstrated good biocompatibility and established a stable electric field during mechanical stretching. PC12 cells showed enhanced proliferation rate and axon outgrowth under electrical stimulation alone, and the cell number significantly increased with higher electrical stimulation intensity. The involvement of mechanical stretching in electrical stimulation reduced the cell proliferation rate and axon outgrowth, compared with the case of electrical stimulation alone. Interestingly, the cellular axons outgrowth was found to depend on the stretching direction, where the axons prefer to align perpendicularly to the stretch direction. These results suggested that AgNWs/PDMS electrodes provide an in vitro platform to investigate the effects of electromechanical stimulation on nerve cell behaviors and can be potentially used for nerve regeneration in the future.

Highlights

The nervous system, composed of the central nervous system and the peripheral nervous system, is a vast conductive network that coordinates actions and sensory information of the human body through the transmission of electrical signals to and from different tissues
AgNWs/PDMS electrode was developed to investigate the effects of electromechanical stimulation on PC12 cell proliferation and axon outgrowth
The use of the PDMS model prevented the leak of toxic byproducts and provided sufficient mechanical strength and high elasticity to protect the AgNWs from breaking during stretching (Figure 2), which provided a promising platform to investigate the effects of electromechanical stimulation on PC12 cell proliferation and axon outgrowth

Summary

Introduction

The nervous system, composed of the central nervous system and the peripheral nervous system, is a vast conductive network that coordinates actions and sensory information of the human body through the transmission of electrical signals to and from different tissues. The central nervous system includes the brain and the spinal cord; while the peripheral nervous system is composed of numerous long fibers or axons, which connect with the central nervous system. Peripheral nervous injuries (PNI) have become a common clinical disease, with millions of cases happening annually around the world, and more than 200,000 repair surgeries are performed in the US every year (Du et al, 2018). The PNI generally causes a poor prognosis due to the complicated treatments and high morbidity. About 60% of PNI patients have poor rehabilitation of exercise abilities, and some of them require long-term care by others, which significantly affects patients’ life quality (Gu et al, 2011; Wieringa et al, 2018). It is of great importance to develop effective PNI repair strategies

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Conclusion