Basic—Alimentary TractAdipose-Derived Mesenchymal Stem Cells Alleviate Experimental Colitis by Inhibiting Inflammatory and Autoimmune Responses
Section snippets
Cell Preparation
hASCs and mASCs were obtained and characterized as described in Supplementary Methods and Supplementary Figure 1 (see supplemental material online at www.gastrojournal.org).3, 12
Induction of Colitis and Study Design
To induce colitis, trinitrobenzene sulfonic acid (TNBS, 3 or 5 mg; Sigma, St Louis, MO) in 50% ethanol (100 μL) was administered intrarectally in BALB/c mice. Control mice received 50% ethanol alone. Animals were treated intraperitoneally with medium or with different numbers (105–106 cells/mouse) of hASCs, allogeneic
hASC Injection Protects Against TNBS-Induced Colitis
Recent studies have characterized the immunoregulatory activity of hASCs on T cells.3, 12, 13, 16 Therefore, we first investigated the potential therapeutic action of hASCs in an experimental model of colitis induced by intrarectal infusion of TNBS, which displays human CD-like clinical, histopathologic, and immunologic features.15 TNBS-treated mice developed a severe illness characterized by bloody diarrhea, rectal prolapse, pancolitis accompanied by extensive wasting syndrome, and profound
Discussion
In the present study, we showed that hASCs are able to suppress xenogeneic immune responses and provide a highly effective treatment for TNBS-induced colitis, a murine experimental model of CD. A single systemic injection of hASCs at the onset of the disease ameliorated the clinical and histopathologic severity of the wasting disease, abrogating body weight loss, diarrhea, and intestinal inflammation, and reducing the high mortality caused by this syndrome. Of obvious therapeutic importance is
Acknowledgements
The authors thank Dr Antonio Bernad and the research and development team at Cellerix for their critical reading of the manuscript.
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M.A.G. and E.G.-R. contributed equally to this report.
Conflicts of interest The authors disclose the following: The results presented in this report are part of patent applications by Cellerix. M.A.G., D.B., and M.D. are inventors. Because Cellerix SA and/or the inventors and/or their institutes stand to profit from this work, the authors have a conflict of interest, which hereby has been officially disclosed to the public.
Funding Supported by Ministry of Health, Ministry of Education and Science (PETRI), Cellerix SA, Junta de Andalucia, and RETICS. D.B. is the recipient of a Marie Curie International Integration Grant.