Administration of Schwann Cell‐Like Cells Differentiated From Tonsil‐Derived Mesenchymal Stem Cells Promotes Peripheral Nerve Regeneration by Inducing Macrophage Polarization in a Chronic Constriction Injury Model

INTRODUCTION/AIMS: Schwann cell-like cells (TMSC-SCs) differentiated from human tonsil-derived mesenchymal stem cells (TMSCs) secrete many factors related to nerve regeneration. This study aimed to explore the potential of TMSC-SCs as a therapeutic agent for peripheral nerve regeneration using an animal model of chronic constriction injury (CCI) of peripheral nerves. METHODS: In this study, TMSCs or TMSC-SCs mixed with fibrin glue were administered to the sciatic nerves of CCI rats and observed for 2-8 weeks (Experiment 1). In addition, the mixture with fibrin glue and low- or high-dose TMSC-SCs (TMSC-SC-L or TMSC-SC-H) was administered to the same site and observed for 2-4 weeks (Experiment 2). After administration, peripheral nerve and gastrocnemius muscle regeneration and recovery of motor function were confirmed through nerve conduction studies and histopathological observations. The expression of M1 and M2 macrophage markers was examined after TMSC-SC treatment. RESULTS: Based on nerve conduction studies, myelination assessments, and gastrocnemius muscle observations, the TMSC-SC-H-treated group showed a significant regeneration effect compared with the TMSC or TMSC-SC-L-treated group. Additionally, compared to the TMSC-SC-L group (M1: 1.02 ± 0.15, M2: 0.73 ± 0.06), downregulation of M1 and upregulation of M2 macrophage markers were observed in the TMSC-SC-H group (M1: 0.47 ± 0.03, M2: 1.04 ± 0.11) by Western blotting. DISCUSSION: These results suggest that TMSC-SCs could be developed as an allogeneic therapeutic agent to improve peripheral nerve regeneration in patients with peripheral nerve injury. These findings could serve as a test method to address unmet clinical needs for peripheral nerve regeneration.