{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:13:06Z","timestamp":1778685186490,"version":"3.51.4"},"reference-count":49,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"unspecified","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Wellcome Leap HOPE program","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["K99DE030084"],"award-info":[{"award-number":["K99DE030084"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["K00CA253759"],"award-info":[{"award-number":["K00CA253759"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["T32CA136432"],"award-info":[{"award-number":["T32CA136432"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI190369"],"award-info":[{"award-number":["1R01AI190369"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,4,18]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The scarcity of primary conventional dendritic cells (cDCs) and the limited functionality of monocyte-derived dendritic cells (moDCs) have long hindered mechanistic and translational studies in human dendritic cell (DC) biology and immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We developed a feeder-free differentiation platform to generate CD1c\n                      <jats:sup>+<\/jats:sup>\n                      CD141\n                      <jats:sup>+<\/jats:sup>\n                      human pluripotent stem cell-derived conventional dendritic cells (hPSC-cDCs) to provide a scalable source of DCs with defined properties. A Design-of-Experiments (DoE) optimization strategy was applied to refine cytokine and serum conditions, with the goal of enhancing differentiation efficiency while reducing cytokine demand. The resulting hPSC-cDCs were phenotypically, transcriptionally, and functionally characterized in comparison with primary cDC subsets and moDCs. Functional assays assessed antigen uptake, cytokine production, and the ability to prime antigen-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The optimized protocol increased hPSC-cDC yield by more than twofold while reducing cytokine usage. hPSC-cDCs expressed canonical cDC2 markers and aligned transcriptionally with primary cDC2s. These cells exhibited efficient phagocytic activity, robust cytokine secretion in response to poly(I:C) or combined Toll-like receptors agonists, and a partially activated basal state resembling primary CD1c\n                      <jats:sup>+<\/jats:sup>\n                      CD141\n                      <jats:sup>+<\/jats:sup>\n                      DCs in human tissues. Functionally, hPSC-cDCs induced stronger antigen-specific CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell proliferation, activation, and effector differentiation than moDCs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This feeder-free and DoE-optimized system enables reproducible, large-scale generation of functional hPSC-cDCs that phenotypically and transcriptionally resemble primary cDC2s while exhibiting stronger T-cell priming capacity than moDCs. The platform provides a defined and scalable resource for mechanistic studies, vaccine development, and ex vivo T-cell expansion for cancer immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014402","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T14:30:26Z","timestamp":1778682626000},"page":"e014402","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Feeder-free generation of functional dendritic cells from human pluripotent stem cells"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4342-4105","authenticated-orcid":false,"given":"Wei-Hung","family":"Jung","sequence":"first","affiliation":[{"name":"John A Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA"},{"name":"Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, 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