Generation of Immunogenic Dendritic Cells from Human Embryonic Stem Cells without Serum and Feeder Cells

Tseng, Su-Yi; Nishimoto, Kevin; Silk, Kathryn M.; Majumdar, Anish Sen; Dawes, Glenn; Waldmann, Herman; Fairchild, Paul J.; Lebkowski, Jane; Reddy, Anita

doi:10.2217/rme.09.25

Cited by 56 publications

(62 citation statements)

References 23 publications

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“…Previous studies have established methods of generating DCs from PSCs, and demonstrated the utility of PSC-derived DCs in cancer immunotherapy (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). However, generating a large number of DCs from ESCs or iPSCs has required a scaling-up of the initial volume of undifferentiated PSCs.…”

Section: Introductionmentioning

confidence: 99%

Generation of Mouse Pluripotent Stem Cell–Derived Proliferating Myeloid Cells as an Unlimited Source of Functional Antigen-Presenting Cells

Zhang

Liu

Senju

et al. 2015

Cancer Immunology Research

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The use of dendritic cells (DC) to prime tumor-associated antigen-specific T-cell responses provides a promising approach to cancer immunotherapy. Embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) can differentiate into functional DCs, thus providing an unlimited source of DCs. However, the previously established methods of generating practical volumes of DCs from pluripotent stem cells (PSC) require a large number of PSCs at the start of the differentiation culture. In this study, we generated mouse proliferating myeloid cells (pMC) as a source of antigen-presenting cells (APC) using lentivirus-mediated transduction of the c-Myc gene into mouse PSC-derived myeloid cells. The pMCs could propagate almost indefinitely in a cytokine-dependent manner, while retaining their potential to differentiate into functional APCs. After treatment with IL4 plus GM-CSF, the pMCs showed impaired proliferation and differentiated into immature DC-like cells (pMC-DC) expressing low levels of major histocompatibility complex (MHC)-I, MHC-II, CD40, CD80, and CD86. In addition, exposure to maturation stimuli induced the production of TNFα and IL12p70, and enhanced the expression of MHC-II, CD40, and CD86, which is thus suggestive of typical DC maturation. Similar to bone marrow–derived DCs, they stimulated a primary mixed lymphocyte reaction. Furthermore, the in vivo transfer of pMC-DCs pulsed with H-2Kb-restricted OVA257-264 peptide primed OVA-specific cytotoxic T cells and elicited protection in mice against challenge with OVA-expressing melanoma. Overall, myeloid cells exhibiting cytokine-dependent proliferation and DC-like differentiation may be used to address issues associated with the preparation of DCs. Cancer Immunol Res; 3(6); 668–77. ©2015 AACR.

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Section: Introductionmentioning

confidence: 99%

Generation of Mouse Pluripotent Stem Cell–Derived Proliferating Myeloid Cells as an Unlimited Source of Functional Antigen-Presenting Cells

Zhang

Liu

Senju

et al. 2015

Cancer Immunology Research

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“…After this report, Su and colleagues [16] and also Tseng and colleagues [17] reported similar methods of EB-mediated generation of DC from human ES cells.…”

Section: Generation Of DC From Human Es Cells Based On Eb Formationmentioning

confidence: 90%

“…In addition, clusters of floating cells (Fig. 3e) of the latter type were observed after days [17][18][19], and the cell clusters gradually increased. Addition of maturation stimuli, IL-4, TNF-a, plus anti-CD40 antibody or LPS, to the cells resulted in typical morphology of mature DC (Fig.…”

Section: Generation Of Dendritic Cells From Mouse Es Cellsmentioning

confidence: 92%

Pluripotent stem cells as source of dendritic cells for immune therapy

et al. 2010

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Dendritic cells (DC) are the most potent antigen-presenting cells. In vivo transfer of antigen-bearing DC has proven efficient in priming T cell responses specific to the antigen. DC-based cellular vaccination is now regarded as a powerful means for immunotherapy, especially for anti-cancer immunotherapy. Clinical trials of therapy with DC pulsed with peptide antigens or genetically modified to present antigens are currently carried out in many institutions. In addition, antigen-specific negative regulation of immune response by DC is considered to be a promising approach for treatments of autoimmune diseases and also for regulation of allo-reactive immune response causing graft rejection and GVHD in transplantation medicine. DC for transfer therapy are now generated by in vitro differentiation of peripheral blood monocytes of the patients. However, there is a limitation in the number of available monocytes, and the DC-differentiation potential of monocytes varies depending on the blood donor. Embryonic stem (ES) cells possess both pluripotency and infinite propagation capacity. We consider ES cells to be an ideal source for DC to be used in immunotherapy. Several groups, including us, have developed methods to generate DC from ES cells. This review introduces the studies on generation, characterization, and genetic modification of DC derived from ES cells or induced pluripotent stem (iPS) cells. The issues to be resolved before clinical application of pluripotent stem cell-derived DC will also be discussed.

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“…In a collaborative effort scientists from Geron, CA, USA (www.geron.com), and Oxford University, UK, demonstrated that dendritic cells (DCs) scalably manufactured from hESCs exhibit the normal functions of naturally occurring human DCs found in the bloodstream [3]. The defined protocol for generating hESCderived DCs described in the current study is a stepwise process in which hESCs are first differentiated into monocytic cells, and then converted to immature DCs.…”

Section: Geronmentioning

confidence: 96%

Industry Report

Ilić

2009

Regen. Med.

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Generation of Immunogenic Dendritic Cells from Human Embryonic Stem Cells without Serum and Feeder Cells

Abstract: 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.

Cited by 56 publications

References 23 publications

Generation of Mouse Pluripotent Stem Cell–Derived Proliferating Myeloid Cells as an Unlimited Source of Functional Antigen-Presenting Cells

Generation of Mouse Pluripotent Stem Cell–Derived Proliferating Myeloid Cells as an Unlimited Source of Functional Antigen-Presenting Cells

Pluripotent stem cells as source of dendritic cells for immune therapy

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