{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:04:56Z","timestamp":1779174296020,"version":"3.51.4"},"reference-count":18,"publisher":"Cambridge University Press (CUP)","issue":"11","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Current liver-stage\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    models are complex, expensive and largely inaccessible, hindering research progress. Here, we show that a 3D liver spheroid model grown from immortalized HepG2\/C3A cells supports the complete intrahepatocytic lifecycle of\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    . Our results demonstrate sporozoite infection, development of exoerythrocytic forms and breakthrough infection into erythrocytes. The 3D-grown spheroid hepatocytes are structurally and functionally polarized, displaying enhanced albumin and urea production and increased expression of key metabolic enzymes, mimicking\n                    <jats:italic>in vivo<\/jats:italic>\n                    conditions \u2013 relative to 2D cultures. This accessible, reproducible model lowers barriers to malaria research, promoting advancements in fundamental biology and translational research.\n                  <\/jats:p>","DOI":"10.1017\/s0031182025100322","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T07:25:44Z","timestamp":1750404344000},"page":"1127-1134","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":2,"title":["An accessible 3D HepG2\/C3A liver spheroid model supporting the complete intrahepatocytic lifecycle of\n                    <i>Plasmodium falciparum<\/i>"],"prefix":"10.1017","volume":"152","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5546-9346","authenticated-orcid":false,"given":"Claire H.","family":"Caygill","sequence":"first","affiliation":[{"name":"Liverpool School of Tropical Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salwa Omar","family":"Alqurashi","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Adolfi","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Carson","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelika","family":"Sturm","sequence":"additional","affiliation":[{"name":"TropIQ Health Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel S.","family":"Evans","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jess B.","family":"Jinks","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koen J.","family":"Dechering","sequence":"additional","affiliation":[{"name":"TropIQ Health Sciences"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Reimer","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaun H.","family":"Pennington","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parveen","family":"Sharma","sequence":"additional","affiliation":[{"name":"Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen A.","family":"Ward","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6356-6595","authenticated-orcid":false,"given":"Giancarlo A.","family":"Biagini","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"S0031182025100322_ref1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014275"},{"key":"S0031182025100322_ref8","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-023-00772-9"},{"key":"S0031182025100322_ref18","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222312808"},{"key":"S0031182025100322_ref6","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-99152-9"},{"key":"S0031182025100322_ref4","doi-asserted-by":"publisher","DOI":"10.1039\/C6TX00101G"},{"key":"S0031182025100322_ref5","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-013-1078-5"},{"key":"S0031182025100322_ref9","doi-asserted-by":"publisher","DOI":"10.3390\/cells9122557"},{"key":"S0031182025100322_ref3","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.096"},{"key":"S0031182025100322_ref7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04221-9"},{"key":"S0031182025100322_ref11","doi-asserted-by":"publisher","DOI":"10.1126\/science.781840"},{"key":"S0031182025100322_ref2","doi-asserted-by":"publisher","DOI":"10.3389\/fmedt.2020.611913"},{"key":"S0031182025100322_ref17","doi-asserted-by":"publisher","DOI":"10.1101\/2023.01.05.522945"},{"key":"S0031182025100322_ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2022.05.014"},{"key":"S0031182025100322_ref16","unstructured":"World Malaria Report (2023) Geneva: World Health Organization; 2023. Licence: CC BY-NC-SA 3.0 IGO."},{"key":"S0031182025100322_ref13","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-022-01147-0"},{"key":"S0031182025100322_ref12","first-page":"e61426","article-title":"Plasmodium falciparum gametocyte culture and mosquito infection through artificial membrane feeding","volume":"161","author":"Tripathi","year":"2020","journal-title":"Journal of Visualized Experiments: JoVE"},{"key":"S0031182025100322_ref10","first-page":"3","volume-title":"Advances in Pharmacology","author":"Tornio","year":"2018"},{"key":"S0031182025100322_ref14","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00127"}],"container-title":["Parasitology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0031182025100322","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:58:45Z","timestamp":1769605125000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0031182025100322\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,20]]},"references-count":18,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["S0031182025100322"],"URL":"https:\/\/doi.org\/10.1017\/s0031182025100322","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.11.06.621813","asserted-by":"object"}]},"ISSN":["0031-1820","1469-8161"],"issn-type":[{"value":"0031-1820","type":"print"},{"value":"1469-8161","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,20]]},"assertion":[{"value":"\u00a9 Liverpool School of Tropical Medicine, 2025. Published by Cambridge University Press.","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http:\/\/creativecommons.org\/licenses\/by\/4.0), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}