This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Su, Z. Articles by Vieweg, J. PubMed PubMed Citation Articles by Su, Z. Articles by Vieweg, J.

Differentiation of Human Embryonic Stem Cells into Immunostimulatory Dendritic Cells under Feeder-Free Culture Conditions

Authors' Affiliation: Department of Urology, College of Medicine, University of Florida, Gainesville, Florida

Requests for reprints: Zhen Su, Department of Urology, University of Florida, College of Medicine, Health Science Center, Box 100247, Gainesville, FL 32610. Phone: 352-273-8236; Fax: 352-273-8335; E-mail: zhen{at}urology.ufl.edu.

Purpose: The objective of this study was to develop a scalable and broadly applicable active immunotherapy approach against cancer, circumventing the limitations typically encountered with autologous vaccination strategies. We hypothesized that human embryonic stem cells (hESC) can serve as a virtually unlimited source for generating dendritic cells (DC) with potent antigen-presenting function. Here, we investigated the developmental processes and requirements for generating large numbers of mature, antigen-presenting DC from pluripotent hESC.

Experimental Design: A feeder cell-free culture system was developed to differentiate hESC into mature DC sequentially through hematopoietic and myeloid precursor stages.

Results: Using this method, we were able to yield large numbers of mature immunostimulatory DC from hESC to enable clinical investigation. Upon activation, the hESC-derived DC secreted interleukin-12p70, migrated in response to MIP-3β, and exhibited allostimulatory capacity. Most importantly, antigen-loaded, hESC-derived DC were capable of stimulating potent antigen-specific CD8⁺ T-cell responses in an HLA class I–matched semiallogeneic assay system. Moreover, HLA class II–mismatched hESC-derived DC induced a potent Th1-type cytokine response without expanding FOXP3⁺ regulatory T cells in vitro.

Conclusions: These data suggest the development of a novel active immunotherapy platform to stimulate potent T-cell immunity in patients with intractable diseases, such as cancer or viral infection.