Repository of Research and Investigative Information

Repository of Research and Investigative Information

Rafsanjan University of Medical Sciences

Combination therapy of mesenchymal stromal cells and sulfasalazine attenuates trinitrobenzene sulfonic acid induced colitis in the rat: The S1P pathway

(2018) Combination therapy of mesenchymal stromal cells and sulfasalazine attenuates trinitrobenzene sulfonic acid induced colitis in the rat: The S1P pathway. Journal of Cellular Physiology. ISSN 1097-4652 (Electronic) 0021-9541 (Linking)

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Official URL: https://www.ncbi.nlm.nih.gov/pubmed/30580446

Abstract

Adipose derived mesenchymal stem cells (ASCs) transplantation is a novel immunomodulatory therapeutic tool to ameliorate the symptom of inflammatory bowel disease (IBD). The objective of this study was to investigate the therapeutic effects of combined sufasalazine and ASCs therapy in a rat model of IBD. After induction of colitis in rats, ASCs were cultured and intraperitoneally injected (3 x 10(6) cells/kg) into the rats on Days 1 and 5 after inducing colitis, in conjunction with daily oral administration of low dose of sulfasalazine (30 mg/kg). The regenerative effects of combination of ASCs and sulfasalazine on ulcerative colitis were assessed by measuring body weight, colonic weight/length ratio, disease activity index, macroscopic scores, histopathological examinations, cytokine, and inflammation markers profiles. In addition, western blot analysis was used to assess the levels of nuclear factor-kappa B (NF-kappaB) and apoptosis related proteins in colitis tissues. Simultaneous treatment with ASCs and sulfasalazine was associated with significant amelioration of disease activity index, macroscopic and microscopic colitis scores, as well as inhibition of the proinflammatory cytokines in trinitrobenzene sulfonic acid (TNBS)-induced colitis. Moreover, combined ASCs and sulfasalazine therapy effectively inhibited the NF-kappaB signaling pathway, reduced the expression of Bax and prevented the loss of Bcl-2 proteins in colon tissue of the rats with TNBS-induced colitis. Furthermore, combined treatment with ASCs and sulfasalazine shifted inflammatory M1 to anti-inflammatory M2 macrophages by decreasing the levels of MCP1, CXCL9 and increasing IL-10, Arg-1 levels. In conclusion, combination of ASCs with conventional IBD therapy is potentially a much more powerful strategy to slow the progression of colitis via reducing inflammatory and apoptotic markers than either therapy alone.

Item Type: Article
Keywords: NF-kappaB adipose derived mesenchymal stem cells inflammation low-dose sulfasalazine
Journal or Publication Title: Journal of Cellular Physiology
Journal Index: Pubmed
Identification Number: https://doi.org/10.1002/jcp.27944
ISSN: 1097-4652 (Electronic) 0021-9541 (Linking)
Depositing User: مهندس مهدی شریفی
URI: http://eprints.rums.ac.ir/id/eprint/4947

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