The Research On NCAM1-induced Protective Effect Of Bone Marrow Derived Mesenchymal Stem Cell(MSC) In Aortic Dissection(AD)

Aortic dissection(AD)is a severe cardiovascular disease characterized by blood penetration through aortic intimal tear into the tunica media and the formation of hematoma extended along aortic wall.The clinical manifestations of AD are complex and varied,endangering patients' safety with a high mortality.Stanford A subtype is extremely dangerous,with a 50%mortality within 48h after onset;and the mortality rate accumulates 1?2%per hour within the first 48h after onset.Although the advancement of imaging and endovascular techniques has significantly improved the diagnosis and therapeutic skills of the disease,patients are still at high risk of death.Stem cell transplantation provides new visions of treatment for many end-stage diseases.Stem cells can be divided into embryonic stem cells(ESCs)and adult stem cells,according to the degree of differentiation.The application of ESCs is limited for unsolvable ethical issues,thus giving adult stem cells tremendous attention.Among them,mesenchymal stem cells(MSCs)are widely used in regenerative medicine,showing giant potential in the treatment of various diseases,for they are free from ethical problems,various in sources and good in immunogenicity.When damage happens,MSCs recruit in the damaged area,participating in tissue repair or replace the damaged tissue.Studies on animals have confirmed that stem cell transplantation can reduce the incidence of AD,or stabilize the existing AD.We studied clinical tissue samples and revealed an aggregation of stem cell in dissected aorta in AD patients,which was in accordance with previous studies.Then we obtained differentially expressed genes and proteins in diseased arteries via microRNA microarray technology and proteomics technology,and verified these genes and molecules that may play a role in the pathogenesis of AD,e.g.SOD and HSP27.When exposed to destructive factors,the aneurysm or dissection begins to form on aorta,and simultaneously the body will initiate a complex self-repair process,trying to rebuild the vessel wall stability.Previous studies have demonstrated the protective effect of MSCs on the pathogenesis of AD.However,the exact mechanism is still unclear,e.g.how does MSCs participate in the 'destructive&constructive' balance;and which pathways or molecules of MSCs are involved.A better understand of the specific pathogenesis of the disease may contribute to early diagnosis and treatment,and provide new options for the treatment.In order to clarify the specific mechanism of MSCs on AD,we performed transcriptome sequencing.By RNA-seq,we obtained differentially expressed genes between MSCs from AD patients(AD-MSCs)and MSCs from healthy donors(HD-MSCs).This differential expression profile reveals up-regulated and down-regulated genes of MSCs in AD pathogenesis.Based on the p-value and fold change(FC),we chose 9 genes to perform quantitative real time polymerase chain reaction(qRT-PCR)for validation.qRT-PCR results were consistent with the trend of RNA-seq results.In addition,KEGG and GO analysis of differentially expressed genes revealed differential pathway and functional enrichment of DEGs.RNA-seq results provide important information for further studies.Then,based on the published literatures,we finally chose differentially expressed gene NCAM1 to perform its funtion on MSCs.Our study showed that NCAM1 gene could significantly increase the migration function of MSCs and enhance the secretion of elastin by SMCs.These effects suggest MSCs plays a protective effect on AD via NCAM1,while the down-regulated NCAM1 in patients' MSCs are related to the pathogensis of AD.Futher studies especially in vivo experiments are needed for validation.