Generation of immunogenic dendritic cells from human embryonic stem cells without serum and feeder cells

Regen Med. 2009 Jul;4(4):513-26. doi: 10.2217/rme.09.25.


Aim: Dendritic cell (DC)-based vaccines have a potential utility for use in the treatment of malignancy. Human embryonic stem cells (hESCs) may provide a more cost-effective and reliable source of DCs for immunotherapy purposes, providing on-demand access for patients.

Method: We developed a protocol to generate DCs from hESCs in vitro in the absence of serum and feeder cells. This protocol uses growth factors bone morphogenetic protein-4, granulocyte macrophage-colony stimulating factor (GM-CSF), stem cell factor and VEGF in serum-free media to generate hESC-derived monocytic cells. These cells are further differentiated to hESC-derived immature DCs with GM-CSF and IL-4, and matured to hESC-derived mature DCs with a maturation cocktail consisting of GM-CSF, TNF-alpha, IL-1beta, IFN-gamma and PGE2.

Results: This study demonstrates the applicability of our defined differentiation process in generating functional hESC-derived DCs from multiple hESC lines. We show that hESC-derived immature DCs phagocytose, process, and present antigen upon maturation. hESC-derived mature DCs express the maturation marker CD83, produce Th1-directing cytokine IL-12p70, migrate in response to chemokine, and activate both viral and tumor antigen-specific T-cell responses.

Conclusion: We developed a chemically defined system to generate unlimited numbers of DCs from hESCs. Our results demonstrate that hESC-derived DCs generated from this process are immunogenic and have the potential to be used for DC immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biotechnology / methods*
  • Bone Morphogenetic Protein 4
  • Cell Differentiation / physiology*
  • Dendritic Cells / cytology*
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / physiology
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Humans
  • Immunotherapy / methods*
  • Stem Cell Factor
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism
  • Telomerase / metabolism
  • Vaccines / biosynthesis*
  • Vascular Endothelial Growth Factor A


  • BMP4 protein, human
  • Bone Morphogenetic Protein 4
  • Stem Cell Factor
  • VEGFA protein, human
  • Vaccines
  • Vascular Endothelial Growth Factor A
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • TERT protein, human
  • Telomerase