Basic And Clinical Research About Treatment Of Traumatic Brain Injury By UC-MSCs

Traumatic brain injury(TBI)is a common neurosurgical disease with high morbidity,mortality and disability rate.With the improvement of stem cell research and technology application,a new therapeutic approach has been proposed-the use of stem cells to treat craniocerebral injury.Among them,human umbilical cord mesenchymal stem cells(hUC-MSCs)have become the first choice of treatment materials for their advantages,such as easy to use the material and have the advantages of both proliferation and differentiation capability.In this study,we use human umbilical cord mesenchymal stem cells as raw materials to treat traumatic brain injury and evaluate their effects in the rat brain trauma model,ischemia-reperfusion model and two cases of craniocerebral trauma cases.On the basis of hUC-MSC transplantation,the pathological and biochemical effects were evaluated,and the potential pathological and therapeutic mechanisms were analyzed and discussed with the latest proteomics methods,therefore which will provide a new idea and theoretical support for the clinical treatment of traumatic brain injury.In this study,hUC-MSCs were successfully isolated from human umbilical cord(wharton's Jelly)and transfected with GFP protein by lentiviral transfection.After labeled hUC-MSCs were stereotaxically transplanted to intraventricular,we found the pathological results of TBI rats transplanted with hUC-MSCs were better than that of the model group.The expression of brain derived neurotrophic factor(BDNF)and glial fibrillary acidic protein(GFAP)were significantly higher than those of the model group;secondly,brain edema usually occurs after TBI.Brain edema will interfere the brain blood supply which will further result in hypoxia.This dual process will finally induce congestive,ischemic and reperfused cerebral ischemia,which namelly the Cerebral Ischemia-Reperfusion injury(CI/R).In this study,the mRNA and protein expression of interleukin-6(IL-6)was down-regulation in hUC-MSC-treated rats after CI/R,while the mRNA and protein expression of BDNF were up-regulation.The results of immunohistochemistry confirmed the same results;In addition,we analyzed CSF samples from two patients with traumatic brain injury using a panoramic,high-throughput method—SWATH.The results of proteomics revealed that a total of 104 proteins showed significant changes after treatment,among which 37 proteins were up-regulation and 67 proteins were down-regulation.In addition,we performed GO functional classifications,COG annotations,and pathway annotations for all detected proteins.We performed GO enrichment and pathway enrichment analysis for all proteins with significant differences in expression levels and found that proteins that differed were more focused on the role of the intercellular proteins and signal transduction proteins,these proteins play a major role in the reconstruction of the intercellular connections.The results of this study demonstrate that the most of hUC-MSCs transplanted in TBI rats can survive in the rat brain and can migrate and home into brain tissue,which can improve the blood supply around the injured tissue,reduce the edema degree of the injured tissue,alleviate the ischemia reperfusion injury,and be beneficial to the recovery of the injured brain tissue.The mechanism may be to regulate the protein which plays a major role in the reconstruction of neural cell connections,increase the factors of brain nutrition,reduce the effect of inflammation,and finally make the injury treated.The results of this study provide an important reference for the study of the plasticity of the central nervous system,thus providing more favorable theoretical support for the clinical treatment of traumatic brain injury.