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bioRxiv · 10.1101/2025.11.13.687739

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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Abstract

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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Jung, W.-H., Khalil, A., Binenbaum, Y., Price, J. M., Vining, K. H., Lungjangwa, T., Sobroal, M. C., Jaenisch, R., Mooney, D. J.. 2025-11-14. Feeder-free generation of functional dendritic cells from human pluripotent stem cells. https://doi.org/10.1101/2025.11.13.687739

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