{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:50:08Z","timestamp":1790621408497,"version":"4.1.0"},"reference-count":31,"publisher":"The Royal Society","issue":"3","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["RO1 DK 064051"],"award-info":[{"award-number":["RO1 DK 064051"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Raab Foundation"},{"name":"The Technical Training Foundation & Ibrahim El Hefni Liver Biorepository"},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"crossref","award":["DP1DA038043-01"],"award-info":[{"award-number":["DP1DA038043-01"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI097552-01A1"],"award-info":[{"award-number":["R01AI097552-01A1"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["Open Biol."],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:p>\n                    Hepatitis C virus (HCV) remains a global public health challenge with an estimated 71 million people chronically infected, with surges in new cases and no effective vaccine. New methods are needed to study the human immune response to HCV since\n                    <jats:italic>in vivo<\/jats:italic>\n                    animal models are limited and\n                    <jats:italic>in vitro<\/jats:italic>\n                    cancer cell models often show dysregulated immune and proliferative responses. Here, we developed a CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell and adult stem cell liver organoid system using a microfluidic chip to coculture 3D human liver organoids embedded in extracellular matrix with HLA-matched primary human T cells in suspension. We then employed automated phase contrast and immunofluorescence imaging to monitor T cell invasion and morphological changes in the liver organoids. This microfluidic coculture system supports targeted killing of liver organoids when pulsed with a peptide specific for HCV non-structural protein 3 (NS3) (KLVALGINAV) in the presence of patient-derived CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells specific for KLVALGINAV. This demonstrates the novel potential of the coculture system to molecularly study adaptive immune responses to HCV in an\n                    <jats:italic>in vitro<\/jats:italic>\n                    setting using primary human cells.\n                  <\/jats:p>","DOI":"10.1098\/rsob.210320","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T03:06:37Z","timestamp":1646190397000},"update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":57,"title":["Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture system"],"prefix":"10.1098","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3668-2803","authenticated-orcid":false,"given":"Vaishaali","family":"Natarajan","sequence":"first","affiliation":[{"name":"The Gladstone Institutes, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9222-8130","authenticated-orcid":true,"given":"Camille R.","family":"Simoneau","sequence":"additional","affiliation":[{"name":"The Gladstone Institutes, San Francisco, CA, USA"},{"name":"Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann L.","family":"Erickson","sequence":"additional","affiliation":[{"name":"Division of General and Transplant Hepatology, California Pacific Medical Center and Research Institute, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5983-3777","authenticated-orcid":false,"given":"Nathan L.","family":"Meyers","sequence":"additional","affiliation":[{"name":"The Gladstone Institutes, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jody L.","family":"Baron","sequence":"additional","affiliation":[{"name":"UCSF Liver Center, University of California San Francisco, San Francisco, CA, USA"},{"name":"Department of Medicine, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart","family":"Cooper","sequence":"additional","affiliation":[{"name":"Division of General and Transplant Hepatology, California Pacific Medical Center and Research Institute, San Francisco, CA, USA"},{"name":"UCSF Liver Center, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd C.","family":"McDevitt","sequence":"additional","affiliation":[{"name":"The Gladstone Institutes, San Francisco, CA, USA"},{"name":"Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5697-1274","authenticated-orcid":false,"given":"Melanie","family":"Ott","sequence":"additional","affiliation":[{"name":"The Gladstone Institutes, San Francisco, CA, USA"},{"name":"UCSF Liver Center, University of California San Francisco, San Francisco, CA, USA"},{"name":"Department of Medicine, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2022,3,2]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-8-161"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.12.010"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11904-018-0404-1"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.08.060"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v25.i29.3929"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines8010090"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.42.2.117"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80044-8"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-199705000-00021"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a036947"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-012-0983-3"},{"key":"e_1_3_6_13_2","first-page":"17","article-title":"Cell culture systems for hepatitis C virus","volume":"369","author":"Steinmann E","year":"2013","unstructured":"Steinmann E, Pietschmann T. 2013 Cell culture systems for hepatitis C virus. Curr. Top. Microbiol. Immunol. 369, 17-48. (doi:10.1007\/978-3-642-27340-7_2)","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a036806"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1268"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.097"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.050"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.06.030"},{"key":"e_1_3_6_19_2","unstructured":"Crignis ED et al. 2020 Human liver organoids: a patient-derived primary model for HBV infection and related hepatocellular carcinoma. bioRxiv 568147."},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002617"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121400109"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22243-7"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.009"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018100300"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.01.054"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.000656"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20036"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.89762"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-019-0812-8"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-021-00210-y"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.14.8687-8697.2005"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.10.5692"}],"container-title":["Open Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsob.210320","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rsob.210320","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsob.210320","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T07:12:30Z","timestamp":1682665950000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/doi\/10.1098\/rsob.210320"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1098\/rsob.210320"],"URL":"https:\/\/doi.org\/10.1098\/rsob.210320","relation":{"has-review":[{"id-type":"doi","id":"10.1098\/RSOB.210320\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.210320\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1098\/RSOB.210320\/v1\/review1","asserted-by":"object"}]},"ISSN":["2046-2441"],"issn-type":[{"value":"2046-2441","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3]]},"assertion":[{"value":"2021-10-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"210320"}}