Primary Study On The Regeneration Of Peripheral Nerves By MSCs-derived Exosomes And Its Mechanism

Objective:Peripheral nerve injury is a common neurological disease,and the effect of repair after peripheral nerve injury is poor.Therefore,finding new methods to improve the repair effect of peripheral nerve injury has always been one of the clinical focuses.Mesenchymal stem cells(MSCs)are a type of pluripotent stem cells that were originally found in the bone marrow.They have multi-directional differentiation potential,hematopoietic support,immune regulation,and self-replication.MSCs secrete a variety of growth factors.The use of endocrine and paracrine to promote tissue repair,with protection of the kidney,reduce myocardial ischemia / reperfusion injury,but also has the potential for the treatment of stroke and Alzheimer's disease,while also promoting the repair of peripheral nerve injury and other effects.Exosomes are nanoscale lipid bilayer vesicles that can be secreted by living cells and contain certain biologically active molecules(such as RNA,m RNA,and many proteins).Bone marrow MSCs can produce abundant exosomes.MSCs-derived exosomes mimic the biological function of certain MSCs and have gradually been shown to promote tissue repair.Whether MSCs promote the repair of peripheral nerve injury is related to the secretion of exosomes.There are few reports in the literature.This article mainly discusses whether MSCs-derived exosomes can promote the regeneration of peripheral nerves and their effects,and preliminary explore the mechanism of the repair process.Methods:The right sciatic nerve crush model was established in SD rats.The right gastrocnemius muscles of model rats were injected with PBS,exosomes and MSCs.(1)Before and 14 days after surgery and 28 days after operation,gait analysis was performed to calculate the sciatic nerve function index(SFI);hot plate test was used to determine the thermal pain latency.(2)On the 14 th and 28 th days after operation,the proximal and distal nerve trunks of the crushing site were taken and toluidine blue staining was used to calculate the number and diameter of myelinated fibers regenerated by the distal nerve.(3)On the 14 th and 28 th days after operation,the distal nerves of the squeezing site were taken and the expression of S-100 and NGF protein was observed by immunohistochemistry.(4)The expression of m RNA of Akt1,NGFr,PMP22,S100 B,VEGFA and HGF m RNA extracted from DRG was detected by Q-PCR after 7 days.Result :(1)On the 14 th and 28 th days after operation,the right hind limbs of the exosomes and MSCs groups showed significantly better motor function,redness,and toe extension than the PBS group.The degree of recovery of SFI and thermal pain latency was significantly better in the exosomal and MSCs groups than in the PBS group(p < 0.05).Among them,the 14-day and 28-day SFI value of exosomes was superior to that of MSCs group.(2)On the 14 th and 28 th days after operation,the number and diameter of regenerated myelinated nerve fibers in the exosomal and MSCs groups were significantly better than those in the PBS group(p < 0.05),14 days and 28 days after operation.The number of nerve fibers in the body group was more than that of the MSCs group(p < 0.05).(3)On the 14 th and 28 th days after operation,the expression of S-100 and NGF in the exosomal and MSCs groups was higher than that in the PBS group(P < 0.05).(4)The m RNA expression of PMP22,VEGFA,NGFr and S100 B in the DRG of exosomal and MSCs groups increased 7days after operation(P < 0.05).Conclusion:(1)MSCs-derived exosomes can promote peripheral nerve regeneration,which is as effective as MSCs.(2)MSCs-derived exosomes can promote the expression of S-100 B,NGFr,PMP-22 and VEGFA in peripheral nerves.