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Improving our understanding of the interactions between human dendritic cells (DCs) and T cells may contribute to the development of therapeutic strategies for a variety of immune-mediated disorders. The possibility of using DCs themselves as tools to manipulate immune responses opens even greater therapeutic avenues. Current methods of generating human DCs are both inadequate and susceptible to high levels of variability between individuals. DCs differentiated from human embryonic stem cells (hESCs) could provide a more reliable, consistent solution. DCs have now successfully been differentiated from hESCs and more recently this has been repeated using protocols that avoid the inclusion of animal products, an important modification for clinical use. We have developed a novel method for the generation of DCs from hESCs in the absence of animal products that does not necessitate a separate embryoid body (EB) generation step. The technique involves the use of four growth factors and their successive removal from culture, resulting in accumulation of DCs with phenotypic, morphological, and immunostimulatory properties comparable to those of classical human monocyte-derived DCs. In addition to the application of hESC-derived DCs in basic research and novel approaches to cancer immunotherapy, they may also play a central role in the field of regenerative medicine. Tolerogenic DCs differentiated from hESCs may be used to persuade the immune system of the recipients of cell replacement therapy to tolerate allogeneic tissues differentiated from the same hESC line. Such an approach may help to address the immunological barriers that threaten to derail the clinical application of hESCs.

Original publication

DOI

10.1007/978-1-61779-201-4_33

Type

Journal article

Journal

Methods Mol Biol

Publication Date

2011

Volume

767

Pages

449 - 461

Keywords

Cell Count, Cell Culture Techniques, Cell Differentiation, Cells, Cultured, Collagen, Colony-Forming Units Assay, Dendritic Cells, Drug Combinations, Embryonic Stem Cells, Fibroblasts, Humans, Laminin, Monocytes, Proteoglycans