Pluripotent stem cells as source of dendritic cells for immune therapy

Abstract

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.

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

“…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.…”

Dendritic cells derived from pluripotent stem cells: Potential of large scale production

“…DC differentiation from hPSCs: promise and progress Similar to deriving HSCs, there are two methods for DC differentiation from hPSCs: (1) through the formation of EBs in suspension culture; and (2) by co-culture with mouse OP9 stromal cell line [54] . The differentiation into DCs starts from mesoderm specification induced by growth factors including vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-4 ( Figure 2) [20,52] .…”

Mesenchymal Stem Cells: Possibilities of New Treatment Options

“…Examples are auditory retinal cells (Jin et al 2009 ;Comyn et al 2010 ;Lamba et al 2010 ;Parameswaran et al 2010 ) , cardiomyocytes (Narazaki et al 2008 ;Pfannkuche et al 2009 ;Tanaka et al 2009 ;Zhang et al 2009b ;CarvajalVergara et al 2010 ;Kaichi et al 2010 ;Martinez-Fernandez et al 2010 ) , insulinsecreting islet-like clusters (Tateishi et al 2008 ) , motor neurons (Dimos et al 2008 ;Ebert et al 2009 ;Hu and Zhang 2009 ;Karumbayaram et al 2009 ) , dopaminergic neurons (Wernig et al 2008 ;Cai et al 2010 ;Swistowski et al 2010 ) , auditory spinal ganglion neurons (Nishimura et al 2009 ) , smooth muscle cells (Taura et al 2009b ;Xie et al 2009 ) , vascular endothelial cells (Taura et al 2009b ) , dendritic cells and macrophages (Senju et al 2009(Senju et al , 2010 , adipocytes (Tashiro et al 2009 ;Taura et al 2009a ) , osteoblasts (Tashiro et al 2009 ) , hematopoietic cells (Hanna et al 2007 ;Eminli et al 2009 ;Kaufman 2009 ;Lu et al 2009 ;Okabe et al 2009 ;Raya et al 2009 ;Kaneko et al 2010 ) , and endothelial progenitor cells (Xu et al 2009 ;Abaci et al 2010 ;…”