{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T11:25:56Z","timestamp":1783077956195,"version":"3.54.6"},"reference-count":16,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2015-03855"],"award-info":[{"award-number":["RGPIN-2015-03855"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["CGS-D: 454402-2014"],"award-info":[{"award-number":["CGS-D: 454402-2014"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["USRA"],"award-info":[{"award-number":["USRA"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Three-dimensional cell culturing to capture a life-like experimental environment has become a versatile tool for basic and clinical research. Mucosal and skin tissues can be grown as \u201corganoids\u201d in a petri dish and serve a wide variety of research questions. Here, we report our experience with human cervical organoids which could also include an immune component, e.g., Langerhans cells. We employ commercially available human cervical keratinocytes and fibroblasts as well as a myeloid cell line matured and purified into langerin-positive Langerhans cells. These are then seeded on a layer of keratinocytes with underlying dermal equivalent. Using about 10-fold more than the reported number in healthy cervical tissue (1\u20133%), we obtain differentiated cervical epithelium after 14 days with ~1% being Langerhans cells. We provide a detailed protocol for interested researchers to apply the described \u201caseptic\u201d organoid model for all sorts of investigations\u2014with or without Langerhans cells.<\/jats:p>","DOI":"10.3390\/v12121375","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T20:06:09Z","timestamp":1606853169000},"page":"1375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Potentials and Pitfalls of a Human Cervical Organoid Model Including Langerhans Cells"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9898-5546","authenticated-orcid":false,"given":"Robert","family":"Jackson","sequence":"first","affiliation":[{"name":"Biotechnology Program, Lakehead University, Thunder Bay, ON P7B 5E1, Canada"},{"name":"Probe Development and Biomarker Exploration, Thunder Bay Regional Health Research Institute, Thunder Bay, ON P7B 6V4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan D.","family":"Lukacs","sequence":"additional","affiliation":[{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingeborg","family":"Zehbe","sequence":"additional","affiliation":[{"name":"Probe Development and Biomarker Exploration, Thunder Bay Regional Health Research Institute, Thunder Bay, ON P7B 6V4, Canada"},{"name":"Department of Biology, Lakehead University, Thunder Bay, ON P7B 5E1, Canada"},{"name":"Northern Ontario School of Medicine, Lakehead University, Thunder Bay, ON P7B 5E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jackson, R., Eade, S., and Zehbe, I. (2019). An epithelial organoid model with Langerhans cells for assessing virus-host interactions. Philos. T. R. Soc. B., 374.","DOI":"10.1098\/rstb.2018.0288"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s004280050173","article-title":"Organotypic culture of HPV-transformed keratinocytes: A model for testing lymphocyte infiltration of (pre)neoplastic lesions of the uterine cervix","volume":"432","author":"Jacobs","year":"1998","journal-title":"Virchows Arch."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/S0002-9440(10)65324-2","article-title":"Colonization of in vitro-formed cervical human papillomavirus-associated (pre)neoplastic lesions with dendritic cells: Role of granulocyte\/macrophage colonystimulating factor","volume":"154","author":"Hubert","year":"1999","journal-title":"Am. J. 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PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101540"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jackson, R., Rosa, B.A., Lameiras, S., Cuninghame, S., Bernard, J., Floriano, W.B., Lambert, P.F., Nicolas, A., and Zehbe, I. (2016). Functional variants of human papillomavirus type 16 demonstrate host genome integration and transcriptional alterations corresponding to their unique cancer epidemiology. BMC Genom., 17.","DOI":"10.1186\/s12864-016-3203-3"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1189\/jlb.0206111","article-title":"A CD34+ human cell line model of myeloid dendritic cell differentiation: Evidence for a CD14+CD11b+ Langerhans cell precursor","volume":"80","author":"Santegoets","year":"2006","journal-title":"J. Leukoc. 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Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1432-0436.1976.tb00890.x","article-title":"A model implicating the Langerhans cell in keratinocyte proliferation control","volume":"5","author":"Potten","year":"1976","journal-title":"Differentiation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0006-291X(03)00060-3","article-title":"Interleukin 15 induces the signals of epidermal proliferation through ERK and PI 3-kinase in a human epidermal keratinocyte cell line, HaCaT","volume":"301","author":"Yano","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.0105-2896.2004.00211.x","article-title":"Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4","volume":"202","author":"Watford","year":"2004","journal-title":"Immunol. 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