Combination therapy of mesenchymal stromal cells and sulfasalazine attenuates trinitrobenzene sulfonic acid induced colitis in the rat: The S1P pathway |
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| Authors: | Aliakbar Yousefi-Ahmadipour Amir Rashidian Mohammad Reza Mirzaei Alireza Farsinejad Fatemeh PourMohammadi-Nejad Mahmoud Ghazi-Khansari Jafar Ai Sadegh Shirian Amir Allahverdi Jamileh Saremi Somayeh Ebrahimi-Barough |
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| Institution: | 1. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran;2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;3. Department of Clinical Biochemistry, Faculty of Medicine Rafsanjan University of Medical Sciences, Rafsanjan, Iran;4. Department of Hematology and Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran;5. Department of Periodontics, School of Dentistry, Rafsanjan University of Medical Sciences, Rafsanjan, Kerman, Iran;6. Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran |
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| 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 × 106cells/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-κB) 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-κB 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. |
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| Keywords: | adipose derived mesenchymal stem cells inflammation low-dose sulfasalazine NF-κB |
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