Abstract

Inflammatory bowel disease (IBD), which main clinical manifestations include abdominal pain and diarrhea occurring repeatedly, is a kind of autoimmune disease. It has been reported in preceding studies that mesenchymal stem cells (MSCs) can reduce inflammation by regulating the function of immune cells. But studies about the interaction between MSCs and adaptive immune cells, especially in IBD models, are insufficient. Therefore, the objective of this research was to estimate the therapeutic effects of MSCs from human umbilical cord blood (hUCB-MSCs) in an IBD model of rodent and to clarify the therapeutic mechanisms of hUCB-MSCs. Dextran sulfate sodium (DSS) was used to induce colitis in rodent. Mice with colitis were treated with intraperitoneal infusions of hUCB-MSCs and evaluated for mortality and diverse disease symptoms containing weight reduction, diarrhea, and bloody stools. The levels of histopathologic severity and generation of regulatory T cells (Treg) were also determined. Treatment with hUCB-MSCs ameliorated the clinical and histopathologic severity of acute and chronic colitis in mice. Furthermore, T cell infiltration into the inflamed colon was significantly decreased (p = 0.0175), and Foxp3+ cells were substantially higher in the hUCB-MSC group than that of the DSS group. Our results suggest that hUCB-MSCs are able to alleviate inflammation via adding Foxp3+ Tregs in an IBD model of mouse. As a result, these findings suggest the opportunity of hUCB-MSC being applied to patients with IBD.

Highlights

  • Inflammatory bowel disease (IBD) is a kind of recurrent-and-remittent disease, which consists of ulcerative colitis and Crohn’s disease, and characterized by intestinal mucosal destruction

  • It was found that hUCB-mesenchymal stem cells (MSCs) could inhibit the proliferation of PBMC stimulated by PHA when co-cultured under cell-cell contact for 4 days at different ratios (Figure 2A)

  • The present study revealed the efficacy of hUCB-MSCs on a mouse model of IBD induced by Dextran sulfate sodium (DSS)

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Summary

Introduction

Inflammatory bowel disease (IBD) is a kind of recurrent-and-remittent disease, which consists of ulcerative colitis and Crohn’s disease, and characterized by intestinal mucosal destruction. Its pathogenesis is related to dysfunctional immune cells and changed inflammatory state. This immune irregularity and inflammation causes mucosal destruction of colon in the end, and some patients even had distal small bowel involvement (Anderson et al, 2013). MSC Alleviate Colitis by Increasing Tregs between T effectors and T regulators (Tregs) causes the expansion of self-reactive T cells and subsequent inflammation (Bouma and Strober, 2003). Using MSCs presents a unique cell-based strategy for the treatment of IBD with the potential to maintain intestinal homeostasis (Qiu et al, 2017)

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