Abstract
BACKGROUND: The use of Schwann cell-like cells (SCLCs) derived from stem cells has been introduced as an effective strategy for promoting peripheral nerve regeneration (PNR). However, molecular mechanisms underlying therapeutic transplantation of SCLCs for PNR are often ignored. OBJECTIVES: To explore the potential of SCLCs for the treatment of sciatic never injury and investigate the underlying molecule mechanisms. METHOD: SCLCs differentiated from human amniotic mesenchymal stem cells (hAMSCs) and specific markers of Schwann cells were detected. SCLCs were transplanted into the injured sites of a rat model of sciatic nerve injury, and sciatic nerve functional index (SFI) was determined. RESULTS: SCLCs expressed specific markers of Schwann cells as well as secreted neurotrophic factors. The transplantation of SCLCs into injured sites of a rat model of sciatic nerve injury promoted the functional recovery. With regard to the underlying molecular mechanisms, we identified c-Jun as a negative regulator of the myelination of SCLCs. Moreover, we discovered a novel signaling transduction pathway in SCLCs; that is, miR-214 directly targets c-Jun to promote the myelination of SCLCs. Finally, we demonstrated that miR-214 upon overexpression in SCLCs enhanced the therapeutic effects of SCLCs on sciatic nerve injury. CONCLUSIONS: We demonstrate that SCLCs have beneficial effect for myelination. Moreover, our results provide a previously unknown molecular basis underlying the treatment of peripheral nerve injury with SCLCs and also offer a practical strategy for future therapeutic promotion of PNR.