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BACKGROUND: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.
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Objective To compare two sources of mesenchymal stem cells ( MSCs) from human placenta and umbilical cord, and to optimize a technical solution for bench or clinical studies of MSCs.Methods MSCs were isolated from human placenta and umbilical cord and expanded for analysis.The cell morphology was observed under invert microscope, the immunophenotypic feature of MSCs was analyzed with flow cytometer, the cell proliferation ability was determined by cell cycle assay and cell doubling time, the cell differentiation potential was evaluated by osteogenic and adipogenic induction in vitro as well.Results Both sources of MSCs were adherent cells and exhibited fusiform and fibrous morphology. Furthermore, both MSCs high expressed CD90 and CD105, and were negative for the markers of CD34, CD45 and HLA-DR.The population doubling time of MSCs form human placenta and umbilical cord was 39.5 h and 40.8 h separately, and the results of cell cycle analysis showed that the percent of the two sources of MSCs in G0/G1 phase was 52.12%and 57.50% respectively. The above results demonstrated that both sources of MSCs possessed the similar biological characteristics in morphology, phenotype and as well as proliferation ability.In addition, both of them could be induced into osteoblasts and adipocytes in vitro.Conclusion MSCs from human placenta have the similar biological characteristics to these from human umbilical cord, and both of them are better candidates for bench and clinical research.
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Objective To investigate the regulatory effects of IFN-γon the expression of pro-grammed death ligand 2 (PDL2) on human placenta mesenchymal stem cells (hPMSCs) and the hPMSCs-induced differentiation of peripheral blood CD 8+IL-10+T cell subsets .Methods hPMSCs were isolated from mature human placenta by enzyme digestion .The expression of PDL2 on hPMSCs and the regulatory effects of IFN-γon PDL2 expression were detected by RT-PCR and flow cytometry ( FCM ) , respectively . Peripheral blood mononuclear cells (PBMCs) were isolated from healthy subjects by density gradient centrif-ugation.T cells were purified with sheep red blood cells .FCM was used to detect the ratios of CD 8+IL-10+T cell subsets in PHA or CD3/CD28 beads activated T cells in the presence of hPMSCs treated with Anti-PDL2 McAb or IFN-γ.Results PDL2 molecules were highly expressed on hPMSCs that could be further enhanced by IFN-γ.The results of FCM demonstrated that hPMSCs could induce the differentiation of CD 8+IL-10+T cell subsets .The ratios of CD8+IL-10+T cell population in T cells activated by different stimulators including PHA and CD3/CD28 beads were significantly increased in the presence of hPMSCs as compared with those without hPMSCs (P<0.01).In addition, the antibody blocking experiments indicated that PDL 2 McAb down-regulated the percentages of CD 8+IL-10+T cell subsets in PHA or CD 3/CD28 beads stimulated T cells in the presence of hPMSCs as compared with those of unblocked groups .CD8+IL-10+T cell subsets were up-regulated in IFN-γtreated hPMSCs groups as compared with those of untreated groups .Conclusion hPMSCs could induce the differentiation of peripheral blood T cells into CD 8+IL-10+T cell subsets , which was enhanced by PDL 2 expressed on hPMSCs .IFN-γcould promote the differentiation of CD 8+IL-10+T cell subsets induced by hPMSCs through up-regulating the expression of PDL2 on hPMSCs.
ABSTRACT
Human placenta-derived stem cells (hPD-SCs) are a mixed group of stem cells.Stem cell medicine has applications for organ damage or failure through regenerative,anti-apoptotic,anti-inflammatory and anti-tumor properties in addition to cell function recovery.Presently,human placenta mesenchymal stem cells (hPMSCs) have similar characteristics to the differentiation of hepatocyte-like cells by promoting hepatocyte regeneration,anti-hepatocyte apoptosis and anti-liver fibrosis,in vitro or in animal models.To further our investigation,a summary of the origin,sorting and biological properties of hPDSCs along with a narration of hPDSCs for liver disease therapy was written.This leads to a discussion for new ideas to further explore cell treatment for liver disease.