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

Figure 1 Schematic comparison between conventional dendritic cell vaccine production and human pluripotent stem cell-based dendritic cell C vaccine production. Conventional dendritic cell (DC) vaccine production is usually from peripheral blood mononuclear cells (PBMCs) in patients. T-flasks, Cell Factories or bags are used for DC maturation. From human pluripotent stem cells (hPSCs), DC precursors (similar to monocytes isolated from PBMCs) can be generated in large scale in bioreactors and then mature into DCs. In theory, this approach can generate an unlimited number of DCs. To stimulate T cell response, the activated DCs can release cytokines such as interleukin (IL)-12 to trigger T helper type 1 (Th1) immune response. DCs are also able to capture and process antigens, converting proteins to peptides that are presented on major histocompatibility complex (MHC) molecules and recognized by T cells. The induced Th1 immune response can target on the cancer cells, which express tumor-specific antigens.

Figure 2 Schematic differentiation process from human pluripotent stem cells to dendritic cells. The differentiation into dendritic cells (DCs) was initiated from mesoderm specification. Then, the cells become hematopoietic stem cells (HSCs) after treatment with growth factors, followed by the stage of more committed common myeloid progenitors (CMP). CMP will then become monocyte-like cells as DC precursors. DC precursors will become immature DCs (iDCs), which further differentiate into mature DCs (mDCs). Definite markers can be used to identify each stage over the course of differentiation. Bry: Mesoderm marker brachyury; BMP-4: Bone morphogenetic protein-4; VEGF: Vascular endothelial growth factor; GM-CSF: Granulocyte-macrophage colony-stimulating factor; SCF: Stem cell factor; IL-4: Interleukin 4; IL1-β: Interleukin-1 beta; IFN-γ: Interferon gamma; PGE-2: Prostaglandin E2; TNF-α: Tumor necrosis factor alpha.