Electrical stimulation of human neural stem cells via conductive polymer nerve guides enhances peripheral nerve recovery

Severe peripheral nerve injuries often result in permanent loss of function of the affected limb. Current treatments are limited by their efficacy in supporting nerve regeneration and behavioral recovery. Here we demonstrate that electrical stimulation through conductive nerve guides (CNGs) enhances...

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Bibliographic Details
Published inBiomaterials Vol. 275; p. 120982
Main Authors Song, Shang, McConnell, Kelly W., Amores, Danielle, Levinson, Alexa, Vogel, Hannes, Quarta, Marco, Rando, Thomas A., George, Paul M.
Format Journal Article
LanguageEnglish
Published Elsevier Ltd 01.08.2021
Subjects
Conductive polymer
Electrical stimulation
Functional recovery
Nerve repair
Stem cells
Electrical stimulation
Conductive polymer
Functional recovery
Stem cells
Nerve repair
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Summary:Severe peripheral nerve injuries often result in permanent loss of function of the affected limb. Current treatments are limited by their efficacy in supporting nerve regeneration and behavioral recovery. Here we demonstrate that electrical stimulation through conductive nerve guides (CNGs) enhances the efficacy of human neural progenitor cells (hNPCs) in treating a sciatic nerve transection in rats. Electrical stimulation strengthened the therapeutic potential of NPCs by upregulating gene expression of neurotrophic factors which are critical in augmenting synaptic remodeling, nerve regeneration, and myelination. Electrically-stimulated hNPC-containing CNGs are significantly more effective in improving sensory and motor functions starting at 1–2 weeks after treatment than either treatment alone. Electrophysiology and muscle assessment demonstrated successful re-innervation of the affected target muscles in this group. Furthermore, histological analysis highlighted an increased number of regenerated nerve fibers with thicker myelination in electrically-stimulated hNPC-containing CNGs. The elevated expression of tyrosine kinase receptors (Trk) receptors, known to bind to neurotrophic factors, indicated the long-lasting effect from electrical stimulation on nerve regeneration and distal nerve re-innervation. These data suggest that electrically-enhanced stem cell-based therapy provides a regenerative rehabilitative approach to promote peripheral nerve regeneration and functional recovery.
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Credit Author Statement
Author contributions: SS designed, performed, and supervised all the experiments reported, analyzed the data, and wrote the manuscript. KM performed the experiments for immunostaining and collected data for immunostaining and histological stains and performed the behavior testing. DA assisted with animal surgeries. AL assisted with animal surgeries and behavior testing. HV provided advice and design of histological experiments and their interpretation. MQ and TAR provided advice, experimental design, and equipment for the gripping test. PMG contributed to design of all experiments, analyzed data and wrote the manuscript.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2021.120982