Kupffer cells-dependent inflammation in the injured liver increases recruitment of mesenchymal stem cells in aging mice

Oncotarget. 2016 Jan 12;7(2):1084-95. doi: 10.18632/oncotarget.6744.

Abstract

Mesenchymal stem cells (MSCs) repair tissue injury and may be used to treat immune associated diseases. In carbon tetrachloride (CCl4)-induced liver injury murine model, we administered MSCs. When MSCs were transmitted to young and old mice with liver injury, more MSCs were recruited in old mice. In old mice, inflammation, characterized by TNF-α and IL-6, was increased due to hyper-activation and hyper-function of Kupffer cells. Blocking Kupffer cells decreased MSCs migration in old mice. In vitro, Kupffer cells isolated from old mice secreted more inflammatory cytokines and chemokines. Thus, hyper-activation of Kupffer cells in old mice increased recruitment of MSCs after their therapeutic administration.

Keywords: Gerotarget; aging; liver injury; mesenchymal stem cells; recruitment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging*
  • Animals
  • Carbon Tetrachloride
  • Cell Movement
  • Cells, Cultured
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / therapy*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression
  • Inflammation / genetics
  • Inflammation / metabolism*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Kupffer Cells / metabolism*
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / metabolism
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Carbon Tetrachloride