Anti-Inflammatory Effects Of Calcitriol-Treated Mesenchymal Stem Cells On Experimental Ulcerative Colitis

Abstract

Objective — Ulcerative colitis is an inflammatory bowel disease usually affecting the innermost lining of the colon and rectum. Both corticosteroids and anti-inflammatory drugs are administrated as medical treatment for UC. However, these drugs, in addition to chemical side effects, impose exorbitant costs on patients. Therefore, extensive studies are underway to find new treatment approaches. This study aims to determine the effect of calcitriol-treated mesenchymal stem cells in the UC treatment. Material and Methods — This experimental study was performed on 50 Wistar rats with inducing ulcerative colitis model by 4% acetic acid. MSCs were isolated from rat bone marrow and proliferated in an appropriate medium. Bone marrow-derived mesenchymal stem cells were injected intraperitoneally. Symptom severity of this disease was evaluated using the factors, such as stool consistency, fecal blood and histopathological study of colon tissue. Furthermore, the levels of myeloperoxidase, nitric oxide and inflammatory cytokines like IL1, IL6 and TNF-α were measured using ELISA technique. Results — The results showed that calcitriol-treated MSCs, significantly reduced the production of inflammatory cytokines including IL-1 (150.22±29.04)(P<0.01), IL-6 (681±56.20)(P<0.01), TNF-α (53.07±11.30)(P<0.01) and significantly decrease in level of NO (12.86±5.65)(P<0.01), MPO (0.175±0.024)(P<0.01) and the destruction of intestinal crypts compared to the control group (P<0.05). Conclusions — It seems that using calcitriol with MSCs has reduced the symptoms of UC in our experimental model. Due to their ease of isolation and expansion, MSCs can be used as an adjunctive therapy to improve the condition of patients with UC colitis.

Animal models of inflammatory bowel disease: category and evaluation indexes

“…These products consist of cytokines and inflammation-related proteins, including some antibodies and enzymes. Interleukin-1 beta, interleukin-6, interleukin-17A, tumor necrosis factor-alpha, and other pro-inflammatory factors are widely used as biomarkers in IBD studies, in which involved molecular signaling pathways are explored too [ 142–146 ]. In order to evaluate the activation of neutrophils and macrophages in intestines of patients with IBD, it is necessary to detect some reactive proteins and enzymes, including lysosomal protein myeloperoxidase [ 134–136 ], C-reactive protein [ 147–149 ], anti-neutrophil cytoplasmic antibodies 45, calprotectin [ 53 , 150 ], and chitinase-3-like protein 1 [ 151 ] in serum or plasma, and calprotectin [ 53 , 150 ], neopterin [ 151 ], neutrophil gelatinase-associated lipocalin, and chitinase-3-like protein 1 in feces or colon tissue.…”