Reactivation of denervated Schwann cells by neurons induced from bone marrow-derived mesenchymal stem cells

Abstract The use of neurons induced from stem cells has been introduced as an effective strategy for promoting peripheral nerve regeneration (PNR). The evolution and role of native denervated Schwann cells (SCs) were often ignored when exploring the mechanisms underlying neural transplantation therapy for PNR. The aim of this study was to understand if following injury, native denervated SCs could be reactivated by transplanting of neurons induced from bone marrow-derived mesenchymal stem cells (NI-BMSCs) to promote PNR. We co-cultured denervated SCs with NI-BMSCs in vitro, tested the proliferation of denervated SCs, and measured the expression and secretion of neurotrophic factors and neural adhesion molecules of the denervated SCs. Concurrently, 48 adult male Sprague-Dawley rats were randomly divided into 4 even groups of 12 rats each: normal group, phosphate-buffered saline (PBS) injection group, BMSCs transplantation group and NI-BMSCs transplantation group. PBS injection and cells transplantation were performed 4 weeks post-injury. After 4 weeks of NI-BMSCs transplantation, the survival of seeded NI-BMSCs was examined, proliferation and ultrastructure of native denervated SCs were detected, and myelination, axonal regeneration and the sciatic functional index measurements were also determinated. Our results demonstrated that NI-BMSCs reactivated denervated SCs both in vitro and in vivo and promoted sciatic nerve regeneration.