| Mesenchymal stem cells(MSCs),as a kind of cell with multidirectional differentiation potential,can differentiate into a variety of cells,such as adipocytes,osteoblasts,chondroblasts and nerve cells.It has been proved that MSCs can also differentiate into tumor fibroblasts and vascular perivascular cells,which play a positive role in tumor progression.MSCs can mainly treat many clinical diseases through paracrine,exosome or direct differentiation,including autoimmune diseases,nervous system diseases,bone marrow transplantation and tumors.The first part of this paper is to study the role and mechanism of CAFs-derived ICAM1 in the progression of colon cancer.Some studies have shown that cancer-associated fibroblasts(CAFs)contribute to the develop-ent and progression of many malignancies.However,the mechanism of CAFs-mediated growth and metastasis of colon cancer still needs to be further studied.In this study,we first established a vitro-cell model of CAFs.We used Exosomes secreted by HCT116 colon cancer cells to promote the differentiation of mesenchymal stem cells into CAFs,and we named MT-CAFs transformed by MSCs.Microarray data analysis and Western Blotting analysis showed that exosomes secreted by HCT116 cells could promote the differentiation of MSCs into MT-CAFs,and the vascular endothelial cell adhesion molecule-1(ICAM1)in MT-CAFs was significantly increased during the differentiation process.In order to verify the role of MT-CAFs-derived ICAM1 in colon cancer,we knocked down the ICAM1 in MT-CAFs,and the knockdown of ICAM1 weakened the effect of MT-CAFs on promoting the growth and invasion of colon cancer cells,which indicates that ICAM1 may be a key molecule in the MT-CAFs-mediated growth and invasion of colon cancer cells.Western Blotting confirmed that ICAM1 could activate STAT3 and AKT signaling pathways in HCT116 cells.Next,Transwell and Wound Healing showed that MT-CAFs secreted ICAM1 promoted the invasion and migration of tumor cells by activating the STAT3 and AKT signaling pathways.These results were further verified in vivo experiments in mice.Finally,we found that ICAM1 was highly expressed in clinical colon cancer specimens and was inversely associated with patient survival.In conclusion,ICAM1 may be one of the key genes in the progression of colon cancer,and is expected to provide a potential therapeutic target for clinical colon cancer patients.The second part of this paper focuses on the efficacy and mechanism of adipose stem cell-derived Exosomes in Parkinson's disease.Parkinson's disease(PD)is the second most widespread neurodegenerative disease in the world.Exosomes from mesenchymal stem cells have been reported to contribute to the recovery of PD.However,its mechanism still needs to be further explored.In this study,time series analysis showed that exosomes from MSCs enabled human microvascular endothelial cells(HBMECs)to be transcriptionally activated and angiogenic genes were significantly elevated.Proteomic analysis of HBMECs treated with exosomes secreted from mesenchymal stem cells revealed a significant increase in intravascular cell adhesion molecule-1(ICAM1).MSCs-derived exosomes can promote the angiogenesis of HBMECs by increasing the expression of ICAM1,thereby alleviating the damage caused by 1-methyl-4-phenylpyridine(MPP+)to HBMECs.When ICAM1 was knocked down,the tube forming ability of HBMECs was significantly reduced.In addition,ICAM1 promotes the angiogenesis of HBMECs by activating the Smad3 and p38MAPK signaling pathways.In a mouse model of PD,exosomes secreted by MSCs were found to promote the recovery of PD,possibly by promoting ICAM1-related angiogenesis.In conclusion,adipose stem cell-derived Exosomes can promote the improvement of PD symptoms,and the possible molecular mechanism is that exosomes-ICAM1-Smad3/p38MAPK axis promotes angiogenesis.This study provides a scientific basis for the treatment of PD with stem cell-derived exosomes. |
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