Mounting evidence implicates that Mesenchymal Stem Cells (MSCs) have properties of low immunogenicity, immunomodulation and anti-inflammatory in vitro and in vivo, especially regulate T-cell responses. Therefore, we transplanted MSCs into an experimental model of IBD to investigate their potential therapeutic effects in vivo. Methods: A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg body weight) was applied
to female BALB/c mice. Bone marrow mesenchymal stem cells (BMSCs) were derived from male green fluorescent protein (GFP) transgenic mice and were transplanted intravenously into animal models after onset of disease. Clinical activity scores, histological changes were evaluated. GFP and Sex determining Region Lumacaftor datasheet Y gene (SRY) expression were used for cell tracking. Ki67 positive cells and Lgr5-expressing cells were detected to observe proliferative activity.
Inflammatory response was determined by measuring levels of different inflammatory mediators in colon and serum. The inflammatory cytokines include tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),interleukin-2(IL-2),IL-6,IL-17,IL-4,IL-10,transforming growth factor(TGF-β).Master regulators of Th1 cell (T-box INK 128 price expressed in T cells,T-bet),Th17 cell(retinoid related orphan receptor gammat,RORγt),Th2 cell (GATA family of transcription factors 3,GATA3) and regulatory T cell O-methylated flavonoid (forkhead box P3,Foxp3) were also detected. Results: Systemic infusion of GFP-BMSCs ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea, inflammation and increasing survival (P < 0.05). Cell tracking
study showed that MSCs homed to the injured colon. MSCs promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cell (P < 0.01). This therapeutic effect was mainly mediated by down-regulating both Th1-Th17 driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt), while by up-regulating Th2 activities (IL-4, IL-10, GATA-3) (P < 0.05). MSCs also induced activated CD4 + CD25 + Foxp3+ regulatory T cells (TGF-β, IL-10, Foxp3) with suppressive capacity on Th1-Th17 effecter responses and promoted Th2 differentiation in vivo (P < 0.05). Conclusion: MSCs emerge as key regulators of immune and inflammatory responses and as an attractive candidate for a cell-based therapy for IBD. Key Word(s): 1. MSCs; 2. IBD; 3. transplantation; 4. immunomodulation; Presenting Author: XUESONG YANG Additional Authors: LIPING ZHANG, WEI FU, AIYING WANG Corresponding Author: XUESONG YANG Affiliations: No Objective: To study the clinical characters and endoscopic manifestation of ulcerative colitis associated colorectal cancer (UC-CRC).
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