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Currently available drug regimens are effective at killing hypnozoites but cause side effects and are difficult to administer. Studies testing drugs for liver-stage malaria remain rare and mainly rely on the use of cancerous or immortalized hepatic cells and primary hepatocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Organoids were used as platform to model liver-stage vivax malaria. Hepatic endoderm cells, endothelial progenitor cells and mesenchymal cells were generated from human induced pluripotent stem cells and self-assembled into liver organoids on top of Matrigel layer. Liver characteristic and maturity were examined through genes and proteins expression of liver markers, and liver functional tests before infected with\n                      <jats:italic>Plasmodium vivax<\/jats:italic>\n                      sporozoites. The infection was then verified by the detection of parasitophorous vacuole membrane proteins, Upregulated in Infectious Sporozoite 4 (UIS4), and blood-stage infection following co-culture with human reticulocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Generated liver organoids showed upregulation of liver specific transcripts including hepatic nuclear factor 4A (\n                      <jats:italic>HNF4A<\/jats:italic>\n                      ), alpha-fetoprotein (\n                      <jats:italic>AFP<\/jats:italic>\n                      ), and albumin (\n                      <jats:italic>ALB<\/jats:italic>\n                      ) which also confirmed by the protein expression. Furthermore, those organoids resembled mature hepatocytes in terms of albumin secretion, fat and glycogen storage and cytochrome activity. Following invasion of\n                      <jats:italic>P. vivax<\/jats:italic>\n                      sporozoites,\n                      <jats:italic>Pv<\/jats:italic>\n                      UIS4 was detected and the hepatic merozoites could develop into ring-stage and early trophozoites in human reticulocytes. Moreover, differential expression patterns of genes involved in lipid and cholesterol synthesis were also detected.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Stem cell-derived liver organoids resemble mature liver cells in terms of liver functions and are susceptible to infection with\n                      <jats:italic>P. vivax<\/jats:italic>\n                      sporozoites, paving the way for studies on the mechanism of hypnozoite formation and testing of possible hypnozoitocidal drugs.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12936-024-05202-8","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T07:19:16Z","timestamp":1733383156000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Human liver organoids are susceptible to Plasmodium vivax infection"],"prefix":"10.1186","volume":"23","author":[{"given":"Norapat","family":"Nitaramorn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Porntida","family":"Kobpornchai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nongnat","family":"Tongkrajang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urai","family":"Chaisri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mallika","family":"Imwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasem","family":"Kulkeaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"5202_CR1","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/s41579-019-0306-2","volume":"18","author":"K Venugopal","year":"2020","unstructured":"Venugopal K, Hentzschel F, Valki\u016bnas G, Marti M. 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Stem Cell Res. 2017;20:91\u20133.","journal-title":"Stem Cell Res"}],"updated-by":[{"DOI":"10.1186\/s12936-025-05632-y","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000}}],"container-title":["Malaria Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-024-05202-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12936-024-05202-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-024-05202-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T19:36:47Z","timestamp":1761680207000},"score":1,"resource":{"primary":{"URL":"https:\/\/malariajournal.biomedcentral.com\/articles\/10.1186\/s12936-024-05202-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,5]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["5202"],"URL":"https:\/\/doi.org\/10.1186\/s12936-024-05202-8","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-4427476\/v1","asserted-by":"object"}]},"ISSN":["1475-2875"],"issn-type":[{"value":"1475-2875","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,5]]},"assertion":[{"value":"15 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 October 2025","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s12936-025-05632-y","URL":"https:\/\/doi.org\/10.1186\/s12936-025-05632-y","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"To generate liver organoids in this study, a human iPSC line, MUSIi001-A, established in a previous study [\n                      \n                      ], was used. Human erythrocytes were obtained from the peripheral venous blood of the subjects after obtaining informed consent. Protocols related to iPSCs, blood collection and cell preparation were approved by the Human Research Protection Unit, Faculty of Medicine Siriraj Hospital, Mahidol University (COA no. Si 953\/2023, 924\/2566(IRB3), and 400\/2567(Exempt)).\n                      P. vivax\n                      sporozoites were used in accordance with biosafety guidelines, and the corresponding protocols were approved by the Faculty of Medicine Siriraj Hospital, Mahidol University (approval no. SI 2024\u2013003).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publications"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"368"}}