Intestinal fibrosis is a common complication in inflammatory bowel disease and leads to functional damage and intestinal obstruction. Intestinal fibrosis is mainly related to the imbalance of deposition and degradation of extracellular matrix components, such as collagens and fibronectins. Studies have found that mesenchymal stem cells secreted soluble bioactive substance such as extracellular vesicles via paracrine action, which exerted marked anti-fibrosis effect.
OBJECTIVE: To investigate the effect of human placenta mesenchymal stem cells-derived extracellular vesicles on collagen deposition in mice with colitis.
METHODS: Totally 24 BALB/c mice were randomly divided into sham operation group, model group and extracellular vesicles group, with 8 mice in each group. Except the sham operation group, the remaining mice of model group and extracellular vesicles group were treated with trinitro-benzene-sulfonic acid to induce intestinal fibrosis, once a day for 6 weeks. The mice in the extracellular vesicles group and model group were administered with extracellular vesicles and phosphate-buffered saline, respectively, at 3 weeks, once a day for 6 weeks. The therapeutic effect of extracellular vesicles was evaluated by disease active index score and the colon weight/length ratio at 1-7 weeks. Diseased intestinal segment was subjected to histological staining. Western blot assay and RT-PCR were used to measure fibrosis related indicators so as to evaluate the degree of intestinal fibrosis.
RESULTS AND CONCLUSION: (1) Compared with the model group, disease active index score and the colon weight/length ratio were significantly reduced, and colonic pathology was significantly improved in the extracellular vesicles group. (2) Compared with the model group, collagen deposition in colon mucosa of mice was significantly reduced, and the expression of collagen I, collagen III and transforming growth factor-β1 decreased significantly in the extracellular vesicles group. (3) Compared with the model group, expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 in mouse colon tissue were significantly increased, while the expression level of tissue inhibitor of metalloproteinase 1 was decreased in the extracellular vesicles group. (4) Results suggest that human placenta mesenchymal stem cells-derived extracellular vesicles can obviously improve the severity of colon injury and reduce the collagen deposition of intestinal mucosa in mice with enteritis.