Abstract

Schwann cells (SCs), which produce neurotropic factors and adhesive molecules, have been reported previously to contribute to structural support and guidance during axonal regeneration; therefore, they are potentially a crucial target in the restoration of injured nervous tissues. Autologous SC transplantation has been performed and has shown promising clinical results for treating nerve injuries and donor site morbidity, and insufficient production of the cells have been considered as a major issue. Here, we performed differentiation of tonsil-derived mesenchymal stem cells (T-MSCs) into SC-like cells (T-MSC-SCs), to evaluate T-MSC-SCs as an alternative to SCs. Using SC markers such as CAD19, GFAP, MBP, NGFR, S100B, and KROX20 during quantitative real-time PCR we detected the upregulation of NGFR, S100B, and KROX20 and the downregulation of CAD19 and MBP at the fully differentiated stage. Furthermore, we found myelination of axons when differentiated SCs were cocultured with mouse dorsal root ganglion neurons. The application of T-MSC-SCs to a mouse model of sciatic nerve injury produced marked improvements in gait and promoted regeneration of damaged nerves. Thus, the transplantation of human T-MSCs might be suitable for assisting in peripheral nerve regeneration.

Highlights

  • Schwann cells (SCs) are the glial cells of peripheral nerves that wrap around axons to form myelin in the peripheral nervous system

  • We confirmed that tonsil-derived mesenchymal stem cells (T-Mesenchymal stem cells (MSCs)) isolated from human palatine tonsils have the ability to differentiate along a glial cell lineage and express cell markers that are typical for glial cells including Schwann Cell (SC)

  • The expression of immature SC markers, Glial Fibrillary Acidic Protein (GFAP) and Nerve Growth Factor Receptor (NGFR), were increased in T-MSC-SC but GFAP expression was shown in undifferentiated T-MSCs to a lesser extent

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Summary

Introduction

Schwann cells (SCs) are the glial cells of peripheral nerves that wrap around axons to form myelin in the peripheral nervous system. SCs are indispensable mediators of repair after nervous tissue injury [2]. They are involved in the pathogenesis of many diseases, including genetic disorders such as Charcot–Marie–Tooth disease, hereditary neuropathy with liability to pressure palsies, and metabolic diseases such as diabetic neuropathy [3,4,5]. SCs have been proposed as a potential cell source for transplantation for functional peripheral nerve recovery. It would be desirable to harvest other cell sources with extensive self-renewal capacity, broad differentiation potential, and readily accessible properties

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