Schwann Cells Enhance Penetration of Regenerated Axons into Three-Dimensional Microchannels
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Nerve regeneration after injury requires proper axon alignment to bridge the lesion site and myelination to achieve functional recovery. Transplanted scaffolds with aligned channels, have been shown to induce axon growth to some extent. However, the penetration of axons into the microchannels remain a challenge, influencing the functional recovery of regenerated nerves. We previously demonstrated that the size of microchannels exerts significant impact on Schwann cells (SCs) migration. Here we demonstrate that migration of SCs promotes, significantly, the dorsal root ganglion (DRG) neurons to extend axons into three-dimensional channels and form aligned fascicular-like axon tracts. Moreover, the migrating SCs attach and wrap around the aligned axons of DRG neurons in the microchannels and initiate myelination. The SCs release growth factors that provide chemotactic signals to the regenerating axons, similar to the response achieved with nerve growth factor (NGF), but with the additional capability of promoting myelination, thereby demonstrating the beneficial effects of including SCs over NGF alone in enhancing axon penetration and myelination in three-dimensional microchannels.
KeywordsNerve regeneration Axon length Schwann cell migration Scaffold Microchannel
We thank Dr. Melinda Frame from the Center for Advanced Microscopy at Michigan State University for help with confocal microscopy imaging. We thank Xiaopeng Bi for their assistance with the photolithography process at Michigan State University. Funding was provided by Division of Chemical, Bioengineering, Environmental, and Transport Systems (Grant Nos. CBET 1510895 and CBET 1547518) and National Cancer Institute (Grant No. R21CA176854).
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Conflict of interest
The authors do not have a conflict of interest to declare. This manuscript has not be submitted elsewhere.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The cell isolation procedures were approved by the Institutional Animal Care and Use Committee at Michigan State University (IACUC no. 10/13-227-00). This article does not contain any studies with human participants performed by any of the authors.
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