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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.

Original publication

DOI

10.2217/rme.09.25

Type

Journal article

Journal

Regen Med

Publication Date

07/2009

Volume

4

Pages

513 - 526

Keywords

Biotechnology, Bone Morphogenetic Protein 4, Cell Differentiation, Dendritic Cells, Embryonic Stem Cells, Flow Cytometry, Granulocyte-Macrophage Colony-Stimulating Factor, Humans, Immunotherapy, Stem Cell Factor, T-Lymphocytes, Telomerase, Vaccines, Vascular Endothelial Growth Factor A