Mesenchymal stem cells alleviate TNBS-induced colitis by modulating inflammatory and autoimmune responses.

AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg body weight) was administered 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 the experimental animals after disease onset. Clinical activity scores and histological changes were evaluated. GFP and Sex determining region Y gene (SRY) expression were used for cell tracking. Ki67 positive cells and Lgr5-expressing cells were determined to measure proliferative activity. Inflammatory response was determined by measuring the levels of different inflammatory mediators in the colon and serum. The inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-6, IL-17, IL-4, IL-10, and transforming growth factor (TGF-ß). Master regulators of Th1 cells (T-box expressed in T cells, T-bet), Th17 cells (retinoid related orphan receptor gamma(t), RORγt), Th2 cells (GATA family of transcription factors 3, GATA3) and regulatory T cells (forkhead box P3, Foxp3) were also determined. RESULTS: Systemic infusion of GFP-BMSCs ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea and inflammation, and increased survival (P < 0.05). The cell tracking study showed that MSCs homed to the injured colon. MSCs promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cells (P < 0.01). This therapeutic effect was mainly mediated by down-regulation of both Th1-Th17-driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt), and by up-regulation of Th2 activities (IL-4, IL-10, GATA-3) (P < 0.05). MSCs also induced activated CD4(+)CD25(+)Foxp3(+) regulatory T cells (TGF-ß, IL-10, Foxp3) with a suppressive capacity on Th1-Th17 effecter responses and promoted Th2 differentiation in vivo (P < 0.05). CONCLUSION: MSCs are key regulators of immune and inflammatory responses and may be an attractive candidate for cell-based therapy of IBD.

[A retrospective study of 22 years endoscopic follow-up in elderly patients with gastrointestinal submucosal tumors].

OBJECTIVE: To observe the occurrence characteristics, dynamic variations and potential risks of smaller gastrointestinal submucosal tumor (SMT) in elderly patients. METHODS: A total of 54 SMT patients were retrospectively recruited from January 1981 to September 2010. There were 51 males (94.4%) and 3 females (5.6%) with an average age of (74 ± 1) years. During each visit, all the relevant data were collected, including symptoms, number of lesion, lesion location, shape, size (maximum transverse diameter under endoscope or endoscopic ultrasonography (EUS), morphology of mucosa, frequency and duration of follow-ups, treatment and pathological results. And the data were analyzed to examine the characteristics of SMT in elderly patients and their dynamic variations. Further more, according to lesion diameter, they were divided into two groups: a diameter ≤ 1 cm (n = 36) and a diameter > 1 cm and ≤ 3 cm (n = 16). Then the change of two groups were observed and compared during the follow-ups. RESULTS: Two cases were not under surveillance after direct surgical resection. The other 52 patients received a follow-up of 22 years. Among them, 5 patients underwent surgical resection for fast-growing tumor and mucosal ulcer. And all their pathologic diagnoses were malignant. Only 1 patient (2.8%) in the diameter ≤ 1 cm group and 4 in the diameter > 1 cm and ≤ 3 cm group turned malignant at 6 years. But, among 4 patients, the shortest interval was merely 14 months. Therefore, compared with the diameter > 1 cm group, the diameter ≤ 1 cm group had a lower rate of malignancy (P < 0.05). CONCLUSIONS: The incidence of smaller SMT (especially diameter ≤ 1 cm) is high in elderly patients, but the malignant potential remains low. Therefore, for elderly patients whose diameters of SMT are no bigger than 3 cm and without obvious malignancy under endoscope or EUS, we may plan an appropriate surveillance interval based on the size of tumor during a long follow-up period.