Human adipose-derived stem cells attenuate inflammatory bowel disease in IL-10 knockout mice

Tissue Cell. 2015 Feb;47(1):86-93. doi: 10.1016/j.tice.2014.12.001. Epub 2014 Dec 6.

Abstract

Inflammatory bowel disease (IBD) is a complex immunological disorder characterized by chronic inflammation caused mainly by unknown factors. The interleukin-10 knockout (IL-10 KO) mouse is a well-established murine model of IBD which develops spontaneous intestinal inflammation that resembles Crohn's disease. In the present study, human adipose-derived mesenchymal stem cells (hAMSCs) were administrated to IL-10 KO mice to evaluate the anti-inflammatory effects of hAMSCs that may attenuate the progress of or treat IBD. After IBD was induced by feeding the IL-10 KO mouse a 125-250 ppm piroxicam mixed diet for 1 week, 2×10(6) hAMSCs were injected into the peritoneum and the mice were switched to a normal diet. After 1 week, the mice were sacrificed and tissue samples were harvested. Tissue scores for inflammation and inflammation-related genes expression were determined. The hAMSC-treated group showed significantly reduced inflammatory changes in histological analysis. Reverse transcription-PCR analysis showed that RANTES, Toll-like receptor 9, and IL-4 expression levels were not significantly different between the groups while IL-12, INF-γ, and TNF-α levels were significantly decreased in the hAMSC treated group. hAMSC attenuated IBD in the IL-10 KO mice by suppressing inflammatory cytokine expression, was mediated by the type 1 helper T cell pathway. Even though only a single injection of hAMSCs was delivered, the effect influenced chronic events associated with inflammatory changes and demonstrated that hAMSCs are a powerful candidate for IBD therapy.

Keywords: Adipose tissue; Inflammatory bowel disease; Interleukin-10; Knockout mice; Mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / transplantation
  • Animals
  • Cell- and Tissue-Based Therapy*
  • Cytokines / biosynthesis
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Humans
  • Inflammation / genetics
  • Inflammation / pathology
  • Inflammation / therapy*
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / pathology
  • Inflammatory Bowel Diseases / therapy*
  • Interleukin-10 / genetics*
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology
  • Mice
  • Mice, Knockout
  • Piroxicam / administration & dosage
  • Toll-Like Receptor 9 / biosynthesis
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Cytokines
  • TLR9 protein, human
  • Toll-Like Receptor 9
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Piroxicam