The Therapeutic Efficacy of Tonsil-derived Mesenchymal Stem Cells in Dextran Sulfate Sodium-induced Acute Murine Colitis Model

Korean J Gastroenterol. 2017 Feb 25;69(2):119-128. doi: 10.4166/kjg.2017.69.2.119.

Abstract

Background/aims: Mesenchymal stem cells (MSCs) are multipotent progenitor cells currently under investigation for its efficacy as the treatment for inflammatory bowel disease. In this study, we evaluated the efficacy of tonsil-derived mesenchymal stem cells (T-MSCs) as a novel source of mesenchymal stem cells and traced their localization in a murine model of acute colitis induced by dextran sulfate sodium (DSS).

Methods: C57BL/6 mice were randomly assigned to the following three groups: the normal control group, DSS colitis group (DSS+phosphate buffered saline), and T-MSC group (DSS+T-MSCs, 1×106). The severity of colitis was assessed by determining the severity of symptoms of colitis, colon length, histopathologic grade, and levels of inflammatory cytokines. T-MSCs labeled with PKH26 were traced in vivo.

Results: The T-MSC group, compared with the DSS colitis group, showed a significantly lower disease activity index (11.3±1.5 vs. 8.3±1.9, p=0.015) at sacrifice and less reduction of body weight (-17.1±5.0% vs. -8.1±6.9%, p=0.049). In the T-MSC group, the histologic colitis score was significantly decreased compared with the DSS colitis group (22.6±3.8 vs. 17.0±3.4, p=0.039). IL-6 and IL-1β, the pro-inflammatory cytokines, were also significantly reduced after a treatment with T-MSCs. In vivo tracking revealed no PKH26-labelled T-MSCs in the colonic tissue of mice with acute colitis.

Conclusions: In the acute colitis model, we demonstrated that the administration of T-MSCs ameliorates inflammatory symptoms and histology. Moreover, the anti-inflammatory activities of T-MSCs were independent of gut homing.

Keywords: Inflammatory bowel disease; Mesenchymal stem cells (MSC); Palatine tonsil.

MeSH terms

  • Acute Disease
  • Animals
  • Body Weight
  • Cells, Cultured
  • Colon / pathology
  • Cytokines / metabolism
  • Dextran Sulfate / toxicity*
  • Disease Models, Animal
  • Humans
  • Inflammatory Bowel Diseases / chemically induced
  • Inflammatory Bowel Diseases / pathology
  • Inflammatory Bowel Diseases / therapy*
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Palatine Tonsil / cytology

Substances

  • Cytokines
  • Interleukin-1beta
  • Interleukin-6
  • Dextran Sulfate