Open AccessGenetically Manipulated Human Embryonic Stem Cell‐Derived Dendritic Cells with Immune Regulatory Function
Author(s) -
Senju Satoru,
Suemori Hirofumi,
Zembutsu Hitoshi,
Uemura Yasushi,
Hirata Shinya,
Fukuma Daiki,
Matsuyoshi Hidetake,
Shimomura Manami,
Haruta Miwa,
Fukushima Satoshi,
Matsunaga Yusuke,
Katagiri Toyomasa,
Nakamura Yusuke,
Furuya Masataka,
Nakatsuji Norio,
Nishimura Yasuharu
Publication year - 2007
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2007-0321
Subject(s) - biology , embryonic stem cell , immune system , antigen , dendritic cell , microbiology and biotechnology , human leukocyte antigen , antigen presenting cell , stem cell , electroporation , major histocompatibility complex , immunology , t cell , genetics , gene
Genetically manipulated dendritic cells (DC) are considered to be a promising means for antigen‐specific immune therapy. This study reports the generation, characterization, and genetic modification of DC derived from human embryonic stem (ES) cells. The human ES cell‐derived DC (ES‐DC) expressed surface molecules typically expressed by DC and had the capacities to stimulate allogeneic T lymphocytes and to process and present protein antigen in the context of histocompatibility leukocyte antigen (HLA) class II molecule. Genetic modification of human ES‐DC can be accomplished without the use of viral vectors, by the introduction of expression vector plasmids into undifferentiated ES cells by electroporation and subsequent induction of differentiation of the transfectant ES cell clones to ES‐DC. ES‐DC introduced with invariant chain‐based antigen‐presenting vectors by this procedure stimulated HLA‐DR‐restricted antigen‐specific T cells in the absence of exogenous antigen. Forced expression of programmed death‐1‐ligand‐1 in ES‐DC resulted in the reduction of the proliferative response of allogeneic T cells cocultured with the ES‐DC. Generation and genetic modification of ES‐DC from nonhuman primate (cynomolgus monkey) ES cells was also achieved by the currently established method. ES‐DC technology is therefore considered to be a novel means for immune therapy. Disclosure of potential conflicts of interest is found at the end of this article.