Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle

Transplantation. 2007 Jan 15;83(1):71-6. doi: 10.1097/


Background: Mesenchymal stem cells (MSCs) play a crucial role in hematopoietic development and have been shown to exert a powerful immunosuppressive effect. In this study, we investigated the effect of bone marrow MSC on the differentiation and function of peripheral blood monocytes into dendritic cells (DCs).

Methods: Human MSCs, generated from normal bone marrow, were added to peripheral blood monocytes stimulated in vitro with granulocyte-macrophage colony stimulating factor and interleukin-4 to become DCs. Monocytes were then examined for the expression of markers characteristic of DCs and their ability to stimulate allogeneic T cells. In addition, the effect of MSCs on the cell cycle of monocyte-derived DCs and the expression of various cell cycle proteins were analyzed by cytometric analysis and Western blotting with specific antibodies.

Results: MSCs blocked the differentiation of monocytes into DCs and impaired their antigen-presenting ability. This resulted from a block of monocytes from entering the G1 phase of the cell cycle with a progressive number of cells accumulating in the G0 phase. Cyclin D2 was downregulated. However, differently from what was observed in T-cells stimulated in the presence of MSCs, the expression of p27 was found decreased, suggesting the involvement of similar but not identical pathways.

Conclusions: We conclude that MSCs impair monocyte differentiation and function by interfering with the cell cycle. These findings imply that MSC-induced immunosuppression might be a side product of a more general antiproliferative effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / analysis
  • Bone Marrow Cells / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Cycle / physiology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Cyclin D2
  • Cyclins / genetics
  • Dendritic Cells / cytology*
  • Dendritic Cells / physiology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Humans
  • Immunophenotyping
  • Interleukin-4 / pharmacology
  • Lymphocyte Activation
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / physiology*
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / physiology


  • Antigens, CD
  • CCND2 protein, human
  • Cyclin D2
  • Cyclins
  • Interleukin-4
  • Granulocyte-Macrophage Colony-Stimulating Factor