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

• Published in: Brain research bulletin Vol. 139; pp. 211 - 223
• Main Authors: Zheng, Yani, Huang, Chao, Liu, Fang, Lin, Haiyan, Niu, Yunfei, Yang, Xiangqun, Zhang, Zhiying
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2018
• Subjects: Animals; Cell Proliferation; Cells, Cultured; Coculture Techniques; Denervated schwann cell; Disease Models, Animal; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells - physiology; Mesenchymal Stem Cells - ultrastructure; Microscopy, Electron, Transmission; Nerve Growth Factors - metabolism; Nerve Regeneration - physiology; Nerve Tissue Proteins - metabolism; Neural Cell Adhesion Molecules - metabolism; Neuron transplantation; Peripheral nerve regeneration; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Reactivation; Recovery of Function - physiology; Schwann Cells - physiology; Schwann Cells - ultrastructure; Sciatic Neuropathy - surgery; Statistics, Nonparametric; Time Factors; Reactivation; Neuron transplantation; Peripheral nerve regeneration; Denervated schwann cell
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2018.03.005

•Neurons were induced from bone marrow-derived mesenchymal stem cells.•Co-culturing neurons reactivated denervated Schwann cells in vitro.•Grafted neurons reactivated native denervated Schwann cells in vivo.•Grafted neurons promoted sciatic nerve regeneration in vivo. 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.