Feeder-free generation of functional dendritic cells from human pluripotent stem cells
Jung, W.-H.; Khalil, A.; Binenbaum, Y.; Price, J. M.; Vining, K. H.; Lungjangwa, T.; Sobroal, M. C.; Jaenisch, R.; Mooney, D. J.
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The scarcity of primary conventional dendritic cells (cDCs) and the limited effectiveness of monocyte-derived dendritic cells (moDCs) have long hindered progress in human dendritic cell research and immunotherapy. We developed a feeder-free differentiation platform that generates CD1c+CD141+ hPSC-cDCs phenotypically aligned with CD141+ tissue-resident cDC2 subsets found in human tissues. We further optimized the differentiation process using a Design-of-Experiments framework to refine cytokine and serum conditions, enhancing differentiation efficiency while reducing cytokine demand. These hPSC-cDCs exhibit efficient antigen uptake, defined cytokine responses, and robust priming of antigen-specific CD8+ T cell proliferation and effector differentiation, outperforming moDCs in direct comparison. Together, this work establishes a robust, and generalizable platform for mechanistic studies and translational development of dendritic cell-based vaccines and standardized ex vivo T cell expansion.
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