Hepatic stellate cells mediate differentiation of dendritic cells from monocytes

J Med Dent Sci. 2012 Mar 13;59(1):43-52.

Abstract

Background: We have previously reported that human umbilical cord blood (UCB)-nucleated cells differentiate into hepatocyte-like cells when cultured in a 5-cytokine cocktail medium. We further found that UCB cells rather differentiated into dendritic-shaped cells by coculture with a human stellate cell (HSC) line, LI90.

Methods: Monocytes from UCB and adult peripheral blood were cocultured with LI90 or rat primary HSCs in a cell-culture insert. Monocytes were also cultured with LI90-conditioned medium containing secreted factors, which were analyzed by a cytokine array.

Results: In the coculture with LI90, resulting dendritic-shaped cells from monocytes expressed dendritic cell (DC) markers and activated allogeneic T cells, indicating that the dendritic-shaped cells were DCs. LI90 in the cytokine cocktail medium secreted various inflammatory factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4. Fibroblast growth factor-2 in the cytokine cocktail was responsible for GM-CSF production from LI90 cells and for differentiation of monocytes into DCs in the LI90 coculture. Moreover, the coculture of monocytes with activated HSCs derived from damaged rat liver induced the differentiation of DCs, whereas quiescent HSCs derived from normal liver scarcely induced such a change.

Conclusion: These results suggest that activated HSCs are involved in differentiation of monocytes into DCs in the liver.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Blood Cells / cytology
  • Cell Culture Techniques
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Chemical and Drug Induced Liver Injury / pathology
  • Coculture Techniques
  • Culture Media, Conditioned
  • Cytokines / pharmacology
  • Dendritic Cells / drug effects
  • Dendritic Cells / physiology*
  • Fetal Blood / cytology
  • Fibroblast Growth Factor 1 / pharmacology
  • Fibroblast Growth Factor 2 / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / analysis
  • Hepatic Stellate Cells / drug effects
  • Hepatic Stellate Cells / physiology*
  • Hepatocyte Growth Factor / pharmacology
  • Humans
  • Interleukin-4 / analysis
  • Lymphocyte Activation / physiology
  • Male
  • Monocytes / drug effects
  • Monocytes / physiology*
  • Rats
  • Rats, Wistar
  • Stem Cell Factor / pharmacology
  • T-Lymphocytes / physiology

Substances

  • Culture Media, Conditioned
  • Cytokines
  • HGF protein, human
  • Stem Cell Factor
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 1
  • Interleukin-4
  • Hepatocyte Growth Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor