Exosomes Derived from ADSCs Promote the Regeneration of Myelin Sheath by Inhibiting SCs Autophagy via miRNA26b Targeting KPNA2

Background: Peripheral nerve injury is encountered quite commonly in the clinic and often results in long-term functional deficits. Investigation toward the development of methods to improve regeneration following nerve injury is ongoing. Numerous studies proved that adipose-derived stem cells (ADSCs) promote the regeneration of peripheral nerve injury, but the mechanism is not clear. Autophagy, highly conserved intracellular process responsible for maintaining cellular homeostasis, and Schwann cells (SCs) play important roles in the regeneration of peripheral nerve injury. Methods: In this study, we explored the effect of ADSC-derived exosomes (ADSC-Exos) on the SCs autophagy and the regeneration of myelin sheath after sciatic nerve injury. Findings: The enhanced autophagy was inhibited, the up-regulated expression of KPNA2 was decreased, and the down-regulated levels of miRNA-26b was increased in injured SCs after treatment with ADSCs-Exos. Usingreal-time PCR, ADSC-Exos were shown to contained a large number of miRNA-26b. The effect of ADSC-Exos inhibiting SCs autophagy were blocked after the over-expression of KPNA2 or the silence of miRNA-26b. Moreover, ADSC-Exos promoted the regeneration of myelin sheaths of injured sciatic nerves in rats. Interpretation: Our results indicate that ADSC-Exos promote the regeneration of myelin sheath by moderately reducing autophagy of injured SCs via miRNA-26b down-regulating KPNA2. Funding Statement: This study was supported by National Key R&D Program of China (2018YFA0107500), National Natural Science Foundation of China (81572146, 31771511), Shanghai Health System Excellent Discipline Leadership Program(2017BR034)and China Postdoctoral Science Foundation (2017M623362, 2018T111131). Declaration of Interests: The authors report no conflicts of interest in this work. Ethics Approval Statement: All animal experiments met the requirements of the Ethics Committee.