Editors' ChoiceNEUROMODULATION

A magnetic look into neuromodulation

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Science Translational Medicine  27 Jun 2018:
Vol. 10, Issue 447, eaau1969
DOI: 10.1126/scitranslmed.aau1969

Abstract

Hydrogel containing magnetic microparticles allows for noninvasive and remote neuromodulation via magnetomechanical stimulation.

Neuromodulation therapy is the direct stimulation of the nervous system through an applied stimulus. Ideally, neuromodulation techniques should be noninvasive, biocompatible, and spatially and temporally controllable. Research investigating techniques for controlling neuromodulation include light, heat, and magnetic stimuli. Currently, these techniques suffer from several limitations including poor tissue penetration, cytotoxicity due to heating, or rely on gene transfection which limit their clinical translation. To address these limitations, Tay and colleagues developed an alternative approach using a three-dimensional (3D) magnetic hydrogel to magnetomechanically stimulate encapsulated neuronal cells. The encapsulated neurons showed increased excitation upon magnetomechanical stimulation in vitro.

The magnetic hydrogel consisted of thiol-functionalized magnetic microparticles (MMPs) within a soft hydrogel material with similar properties to the native brain and spinal cord tissue. Reaction between the hydrogel and MMPs resulted in stable hydrogels with minimal MMP release. The magnetic hydrogel supported healthy neuronal growth, including good viability, proliferation, and neurite outgrowth. To investigate whether the hydrogel could be used for magnetomechanical neuromodulation, neurons were encapsulated in magnetic hydrogels and stimulated with a magnetic field at low frequency and increasing force magnitudes. Magnetomechanical stimulus resulted in a significant increase in Ca2+ influx, suggesting neuronal activation. Based on a number of experiments using inhibitors and electrophysiological recordings, the authors hypothesized that magnetomechanical stimulus induced a Ca2+ influx primarily via the piezo-type mechanosensitive ion channel component 2 (PIEZO2)- and transient receptor potential cation channel subfamily V member 4 (TRPV4)-mediated pathways.

Neuromodulation therapy is a promising approach for a wide range of diseases and injuries, including chronic pain management. Here, the authors present an alternative neuromodulation technique using a magnetomechanical stimulus capable of remotely and noninvasively stimulating neuronal cells or other cells that express mechanosensitive ion channels. Compared with other methods, magnetomechanical stimulation allows for neuromodulation of deep tissues without the need for transfection. Additionally, the proposed approach could be used to probe the role of mechanotransduction in stem cell differentiation and tissue regeneration. It remains to be seen if magnetomechanical simulation will be effective in vivo; however, the study is an important first step toward developing alternative neuromodulation techniques.

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