{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:46:34Z","timestamp":1790549194154,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Patient-derived organoid (PDO) models offer potential to transform drug discovery for inflammatory bowel disease (IBD) but are limited by inconsistencies with differentiation and functional characterization. We profiled molecular and cellular features across a range of intestinal organoid models and examined differentiation and establishment of a functional epithelial barrier.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patient-derived organoids or monolayers were generated from control or IBD patient\u2013derived colon or ileum and were molecularly or functionally profiled. Biological or technical replicates were examined for transcriptional responses under conditions of expansion or differentiation. Cell-type composition was determined by deconvolution of cell-associated gene signatures and histological features. Differentiated control or IBD-derived monolayers were examined for establishment of transepithelial electrical resistance (TEER), loss of barrier integrity in response to a cocktail of interferon (IFN)-\u03b3 and tumor necrosis factor (TNF)-\u03b1, and prevention of cytokine-induced barrier disruption by the JAK inhibitor, tofacitinib.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In response to differentiation media, intestinal organoids and monolayers displayed gene expression patterns consistent with maturation of epithelial cell types found in the human gut. Upon differentiation, both colon- and ileum-derived monolayers formed functional barriers, with sustained TEER. Barrier integrity was compromised by inflammatory cytokines IFN-\u03b3 and TNF-\u03b1, and damage was inhibited in a dose-dependent manner by tofacitinib.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We describe the generation and characterization of human colonic or ileal organoid models capable of functional differentiation to mature epithelial cell types. In monolayer culture, these cells formed a robust epithelial barrier with sustained TEER and responses to pharmacological modulation. Our findings demonstrate that control and IBD patient-derived organoids possess consistent transcriptional and functional profiles that can enable development of epithelial-targeted therapies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izac212","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T18:48:42Z","timestamp":1668106122000},"page":"195-206","source":"Crossref","is-referenced-by-count":72,"title":["Molecular and Functional Characterization of Human Intestinal Organoids and Monolayers for Modeling Epithelial Barrier"],"prefix":"10.1093","volume":"29","author":[{"given":"Scott A","family":"Jelinsky","sequence":"first","affiliation":[{"name":"Pfizer Worldwide Research, Development, and Medical , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merel","family":"Derksen","sequence":"additional","affiliation":[{"name":"HUB Organoids , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Bauman","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research, Development, and Medical , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla S","family":"Verissimo","sequence":"additional","affiliation":[{"name":"HUB Organoids , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wies T M","family":"van Dooremalen","sequence":"additional","affiliation":[{"name":"HUB Organoids , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie Lee","family":"Roos","sequence":"additional","affiliation":[{"name":"HUB Organoids , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Higuera Bar\u00f3n","sequence":"additional","affiliation":[{"name":"HUB Organoids , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Caballero-Franco","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research, Development, and Medical , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryce G","family":"Johnson","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research, Development, and Medical , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle G","family":"Rooks","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research, Development, and Medical , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Pott","sequence":"additional","affiliation":[{"name":"HUB Organoids , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bas","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Centre Utrecht , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G J","family":"Vries","sequence":"additional","affiliation":[{"name":"HUB Organoids , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia F","family":"Boj","sequence":"additional","affiliation":[{"name":"HUB Organoids , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion T","family":"Kasaian","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research, Development, and Medical , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzin","family":"Pourfarzad","sequence":"additional","affiliation":[{"name":"HUB Organoids , Utrecht , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9428-673X","authenticated-orcid":false,"given":"Charles V","family":"Rosadini","sequence":"additional","affiliation":[{"name":"Pfizer Worldwide Research, Development, and Medical , Cambridge, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,10]]},"reference":[{"key":"2023020108373002200_CIT0001","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.crohns.2011.06.009","article-title":"Results from the 2nd scientific workshop of the ECCO. 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