Mesenchymal stem cell transplantation improves chronic colitis-associated complications through inhibiting the activity of toll-like receptor-4 in mice

Guo Chao Niu,Libo Zheng,David Q Shih,Hong Zhang,Lei Liu,Xiaolan Zhang

doi:10.1186/s12876-018-0850-7

Abstract

BackgroundA variety of extra-intestinal manifestations (EIMs), including hepatobiliary complications, are associated with inflammatory bowel disease (IBD). Mesenchymal stem cells (MSCs) have been shown to play a potential role in the therapy of IBD. This study was designed to investigate the effect and mechanism of MSCs on chronic colitis-associated hepatobiliary complications using mouse chronic colitis models induced by dextran sulfate sodium (DSS).MethodsDSS-induced mouse chronic colitis models were established and treated with MSCs. Severity of colitis was evaluated by disease activity index (DAI), body weight (BW), colon length and histopathology. Serum lipopolysaccharide (LPS) levels were detected by limulus amebocyte lysate test (LAL-test). Histology and liver function of the mice were checked correspondingly. Serum LPS levels and bacterial translocation of mesenteric lymph nodes (MLN) were detected. Pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-17A (IL-17A), Toll receptor 4 (TLR4), TNF receptor-associated factor 6 (TRAF6) and nuclear factor kappa B (NF-κB) were detected by immunohistochemical staining, western blot analysis and real-time PCR, respectively.ResultsThe DSS-induced chronic colitis model was characterized by reduced BW, high DAI, worsened histologic inflammation, and high levels of LPS and E. coli. Liver histopathological lesions, impaired liver function, enhanced proteins and mRNA levels of TNF-α, IFN-γ, IL-1β, IL-17A, TLR4, TRAF6 and NF-κB were observed after DSS administration. MSCs transplantation markedly ameliorated the pathology of colon and liver by reduction of LPS levels and proteins and mRNA expressions of TNF-α, IFN-γ, IL-1β, IL-17A, TLR4, TRAF6 and NF-κB.ConclusionsMSCs can improve chronic colitis-associated hepatobiliary complications, probably by inhibition of enterogenous endotoxemia and hepatic inflammation through LPS/TLR4 pathway. MSCs may represent a novel therapeutic approach for chronic colitis-associated hepatobiliary complications.

Highlights

A variety of extra-intestinal manifestations (EIMs), including hepatobiliary complications, are associated with inflammatory bowel disease (IBD)
Isolation and identification of hUC-Mesenchymal stem cells (MSCs) The hUC-MSCs wereisolated from umbilical cords and pooled from a group of four individual donors
UC-MSCs were cultured in the appropriate inducing media for 2 or 3 weeks, and the lipid vacuoles were stained with Oil Red O in the differentiated adipocytes (Fig. 1b), whereas the osteogenic differentiation of MSCs was stained with AlizarinRed (Fig. 1c)

Summary

Introduction

A variety of extra-intestinal manifestations (EIMs), including hepatobiliary complications, are associated with inflammatory bowel disease (IBD). Inflammatory bowel disease (IBD), characterized by chronic, relapsing immune-mediated gut inflammation, is associated with extraintestinal manifestations (EIMs) involving multiple organs. Higher risk has been found in IBD patients with hepatobiliary complications than in normal people [5, 6]. They are common parenteral performances, influencing the fatality rate of IBD. The most common EIMs in IBD are hepatobiliary complications, including primary sclerosing cholangitis (PSC), non-alcoholic fatty liver disease (NAFLD), cholelithiasis, primary biliary cirrhosis (PBC), and IgG4-associated cholangitis (IAC). It is important to investigate the mechanism of chronic colitis-associated hepatobiliary complications

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Discussion

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