CD14+ Monocytes Promote the Immunosuppressive Effect of Human Umbilical Cord Matrix Stem Cells

Exp Cell Res. 2010 Sep 10;316(15):2414-23. doi: 10.1016/j.yexcr.2010.04.018. Epub 2010 Apr 24.

Abstract

Here, the effect of CD14(+) monocytes on human umbilical cord matrix stem cell (hUC-MSC)-mediated immunosuppression was studied in vitro. hUC-MSCs exerted a potent inhibitory effect on the proliferation and interferon-gamma (IFN-gamma) secretion capacities of CD4(+) and CD8(+) T cells in response to anti-CD3/CD28 stimulation. Transwell co-culture system revealed that the suppressive effect was primarily mediated by soluble factors. Addition of prostaglandin synthesis inhibitors (indomethacin or NS-398) almost completely abrogated the immunosuppression activity of hUC-MSCs, identifying prostaglandin E(2) (PGE(2)) as an important soluble mediator. CD14(+) monocytes were found to be able to enhance significantly the immunosuppressive effect of hUC-MSCs in a dose-dependent fashion. Moreover, the inflammatory cytokine IL-1beta, either exogenously added or produced by CD14(+) monocytes in culture, could trigger expression of high levels of PGE(2) by hUC-MSCs, whereas inclusion of the IL-1 receptor antagonist (IL-1RA) in the culture down-regulated not only PGE(2) expression, but also reversed the promotional effect of CD14(+) monocytes and partially restored CD4(+) and CD8(+) T cell proliferation and IFN-gamma secretion. Our data demonstrate an important role of monocytes in the hUC-MSC-induced immunomodulation, which may have important implications in future efforts to explore the clinical potentials of hUC-MSCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Dinoprostone / metabolism
  • Dinoprostone / pharmacology
  • Dinoprostone / physiology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / physiology
  • Humans
  • Immune Tolerance / drug effects
  • Immune Tolerance / physiology*
  • Immunologic Factors / chemistry
  • Immunologic Factors / metabolism
  • Immunologic Factors / pharmacology
  • Inflammation Mediators / pharmacology
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology
  • Interleukin-1beta / physiology
  • Lipopolysaccharide Receptors / metabolism*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / physiology*
  • Mitogens / pharmacology
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monocytes / physiology*
  • Solubility
  • Umbilical Cord / cytology
  • Umbilical Cord / immunology*

Substances

  • Immunologic Factors
  • Inflammation Mediators
  • Interleukin-1beta
  • Lipopolysaccharide Receptors
  • Mitogens
  • Dinoprostone