Endoscopic submucosal injection of adipose-derived mesenchymal stem cells ameliorates TNBS-induced colitis in rats and prevents stenosis

Abstract

BackgroundMesenchymal stem cells have potential applications in inflammatory bowel disease due to their immunomodulatory properties. Our aim was to evaluate the feasibility, safety and efficacy of endoscopic administration of adipose-derived mesenchymal stem cells (ASCs) in a colitis model in rats.MethodsColitis was induced in rats by rectal trinitrobenzenesulfonic acid (TNBS). After 24 h ASCs (107 cells) or saline vehicle were endoscopically injected into the distal colon. Rats were followed for 11 days. Daily weight, endoscopic score at days 1 and 11, macroscopic appearance at necropsy, colon length and mRNA expression of Foxp3 and IL-10 in mesenteric lymph nodes (MLN) were analyzed.ResultsEndoscopic injection was successful in all the animals. No significant adverse events or mortality due to the procedure occurred. Weight evolution was significantly better in the ASC group, recovering initial weight by day 11 (− 0.8% ± 10.1%, mean ± SD), whereas the vehicle group remained in weight loss (− 6.7% ± 9.2%, p = 0.024). The endoscopic score improved in the ASC group by 47.1% ± 5.3% vs. 21.8% ± 6.6% in the vehicle group (p < 0.01). Stenosis was less frequent in the ASC group (4.8% vs. 41.2%, p < 0.01). Colon length significantly recovered in the ASC group versus the vehicle group (222.6 ± 17.3 mm vs. 193.6 ± 17.9 mm, p < 0.001). The endoscopic score significantly correlated with weight change, macroscopic necropsy score and colon length. Foxp3 and IL-10 mRNA levels in MLN recovered with ASC treatment.ConclusionsASC submucosal endoscopic injection is feasible, safe and ameliorates TNBS-induced colitis in rats, especially stenosis.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0837-x) contains supplementary material, which is available to authorized users.

Comparative Analysis between the In Vivo Biodistribution and Therapeutic Efficacy of Adipose-Derived Mesenchymal Stromal Cells Administered Intraperitoneally in Experimental Colitis

“…It has been previously described that the reduction of systemic inflammation in this experimental model of colitis is mediated by the induction of regulatory CD25 + Foxp3 + CD4 + T cells in the colon and mLNs [ 33 , 46 ] together with a reduction in the levels of IL17 in the lamina propria mononuclear cells [ 45 ]. Furthermore, we have recently found that endoscopic administration of eASCs in the colon submucosa of TNBS-colitic rats attenuated the severity of colitis and reduced inflammation, which was associated to increased expression of Foxp3 and IL−10 mRNA in mLNs of eASC-treated rats [ 47 ].…”

Mesenchymal Stromal Cells Anno 2019: Dawn of the Therapeutic Era? Concise Review

“…To clarify this, we performed a comprehensive survey for publications using MSCs in experimental animal models of inflammatory diseases (focusing mainly on sepsis, acute lung injury, acute respiratory distress syndrome, arthritis, and colitis). We identified the methodological details provided in each publication regarding origin and immunological matching of the MSCs used, the status of the cells prior to administration (trypsinized from culture or thawed after cryopreservation), and therapeutic outcome (Supporting Information Table S1; refs: ). Of the 92 publications reviewed, 40 used autologous/syngeneic (43%), 39 xenogeneic (42%), and 7 allogeneic (8%) MSCs (Table ).…”

Mesenchymal stem cells for the treatment of ulcerative colitis: a systematic review and meta-analysis of experimental and clinical studies

“…In terms of the administration routes of MSCs, which might also contribute to the tremendously various outcomes of MSC treatment, our results illustrated that both the delivery of intravenous injections and submucosal injection by endoscopy could be conducive to the healing and recurrence of UC [18]. It is also reported that submucosal endoscopic injection using AD-MSCs could ameliorate TNBS-induced colitis, especially stenosis in rats [54]. Meanwhile, we have noticed from Nam and Cao’s studies that compared with using entire mouse BM-MSCs, application of extracellular vesicles (EVs) extracted from mouse BM-MSCs was more efficient in improving colon length [38, 48].…”