Feeder-free generation of functional dendritic cells from human pluripotent stem cells

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.