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.
Highlights
Mesenchymal stem cells have potential applications in inflammatory bowel disease due to their immunomodulatory properties
In a healthy animal in which adipose-derived mesenchymal stem cells (ASCs) were injected following the same method of the experiment, a dense accumulation of positive cells was observed in the colon submucosa 24 h after the injection, with no signs of immune reaction (Fig. 1d)
Lacking a formal validation, the endoscopic score developed for this study showed a significant correlation with body weight changes, macroscopic damage and colon length, which are commonly used variables in experimental colitis
Summary
Mesenchymal stem cells have potential applications in inflammatory bowel disease due to their immunomodulatory properties. Adult MSCs have been proposed as a potential treatment for Martín Arranz et al Stem Cell Research & Therapy (2018) 9:95 several diseases, including immune-based treatments, due to their multilineage differentiation capabilities that could allow MSCs to repair damaged tissues [1, 3] and their capacity to modulate the function of the majority of immune cells [2, 4] This treatment could promote the regulation of the inflammatory cascade by inducing tolerogenic phenotypes in antigen-presenting cells (APCs) [5] while inhibiting the proliferation of cytotoxic T-cells and promoting differentiation toward regulatory phenotypes in lymphocytes (regulatory T cells) and macrophages (M2 macrophages) [6]. MSCs are considered to have low immunogenicity due to a low expression of major histocompatibility complex (MHC)-I and an absence of MHC-II and classic costimulatory molecules, allowing allogeneic use in the clinical setting or even xenogeneic use for research purposes [10, 11]
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