{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:01:19Z","timestamp":1785427279363,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,13]]},"group-title":"Immunology","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01DK106253"],"award-info":[{"award-number":["R01DK106253"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01DK13370"],"award-info":[{"award-number":["R01DK13370"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01DK133332"],"award-info":[{"award-number":["R01DK133332"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01DK106191"],"award-info":[{"award-number":["R01DK106191"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,13]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Gastric insulin-secreting organoids (GINS) represent a promising source of \u03b2-like cells for type 1 diabetes (T1D) therapy. In same-donor comparisons with induced pluripotent stem cell-derived islets (iPSC-islets), GINS displayed robust glucose responsiveness and reduced expression of key T1D autoantigens. Importantly, GINS exhibited decreased susceptibility to cytotoxicity mediated by engineered HLA-matched preproinsulin-specific effector T cells (Avatar Teffs) and a distinct transcriptional profile enriched for immune-modulatory and stress-adaptive gene programs. To enhance immune evasion, we engineered gastric stem cells to overexpress Programmed Death Ligand 1 (PD-L1) in an inducible manner. PD-L1\n                  <jats:sup>+<\/jats:sup>\n                  GINS maintained normal functionality, while exhibiting improved survival under allogeneic Avatar Teff challenge in a MHC class I-independent fashion. We evaluated PD-L1-mediated protection against autologous Avatar Teff attack using an endothelialized microfluidic platform recapitulating physiologic immune interactions. T cells show reduced infiltration into PD-L1\u207a GINS, resulting in significantly higher organoid viability compared to control GINS. Together, these findings identify GINS as a functional and engineerable \u03b2-like cell platform with intrinsic hypoimmunogenic features, and support PD-L1 engineering as a strategy to enhance immune protection for both allogeneic and autologous transplantation in T1D.\n                <\/jats:p>","DOI":"10.64898\/2026.07.08.736836","type":"posted-content","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T20:45:20Z","timestamp":1783975520000},"source":"Crossref","is-referenced-by-count":0,"title":["Generation of hypoimmunogenic gastric insulin-secreting organoids"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1462-831X","authenticated-orcid":false,"given":"Anna A.","family":"Dattoli","sequence":"first","affiliation":[{"name":"Division of Regenerative Medicine and Hartman Institute for Therapeutic Organ Regeneration, Department of Medicine, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew E.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida Diabetes Institute, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Pearson","sequence":"additional","affiliation":[{"name":"Division of Regenerative Medicine and Hartman Institute for Therapeutic Organ Regeneration, Department of Medicine, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Feinstein","sequence":"additional","affiliation":[{"name":"Division of Regenerative Medicine and Hartman Institute for Therapeutic Organ Regeneration, Department of Medicine, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Lan","sequence":"additional","affiliation":[{"name":"Division of Regenerative Medicine and Hartman Institute for Therapeutic Organ Regeneration, Department of Medicine, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasumati","family":"Polavarapu","sequence":"additional","affiliation":[{"name":"Division of Regenerative Medicine and Hartman Institute for Therapeutic Organ Regeneration, Department of Medicine, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Zhou","sequence":"additional","affiliation":[{"name":"Division of Regenerative Medicine and Hartman Institute for Therapeutic Organ Regeneration, Department of Medicine, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Nachman","sequence":"additional","affiliation":[{"name":"Division of Regenerative Medicine and Hartman Institute for Therapeutic Organ Regeneration, Department of Medicine, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosip","family":"Kelemen","sequence":"additional","affiliation":[{"name":"Division of Regenerative Medicine and Hartman Institute for Therapeutic Organ Regeneration, Department of Medicine, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin","family":"Rafii","sequence":"additional","affiliation":[{"name":"Division of Regenerative Medicine and Hartman Institute for Therapeutic Organ Regeneration, Department of Medicine, Weill Cornell Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remi 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