In:
Regenerative Medicine, Future Medicine Ltd, Vol. 4, No. 4 ( 2009-07), p. 513-526
Abstract:
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-α, IL-1β, IFN-γ 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.
Type of Medium:
Online Resource
ISSN:
1746-0751
,
1746-076X
Language:
English
Publisher:
Future Medicine Ltd
Publication Date:
2009
