{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T19:40:24Z","timestamp":1742413224623,"version":"3.40.1"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Previous cell culture systems using various human hepatoma cell lines established that the intra-hepatic stages of <jats:italic>Plasmodium falciparum<\/jats:italic> could be studied <jats:italic>ex vivo.<\/jats:italic> However, only one of these culture systems yielded infective merozoites that subsequently completed the parasite\u2019s life cycle outside a human host. We hypothesized that a major limitation is the use of laboratory-adapted <jats:italic>P. falciparum<\/jats:italic> blood stages for sporozoites generation. <jats:italic>Plasmodium falciparum<\/jats:italic> sporozoites were generated by membrane-feeding of gametocyte-infected blood samples from hospital patients to <jats:italic>Anopheles arabiensis<\/jats:italic>. Subsequently, cultured HepG2 cells were infected with the sporozoites. From 6 days post-sporozoite inoculation, liver merozoites could be harvested from the cell supernatants. When co-cultured with O<jats:sup>\u2009+<\/jats:sup> erythrocytes, these merozoites established a blood infection and yielded erythrocytic stage parasites that re-infected erythrocytes. To confirm that the erythrocytic parasites generated were <jats:italic>P. falciparum<\/jats:italic>, RNA expressed by the erythrocytic parasites was isolated and used as control in microarray analysis against RNA expressed by irradiated erythrocytic parasites; subsequently, <jats:italic>P. falciparum<\/jats:italic> genes were identified. The cultured HepG2 cells permitted the full intra-hepatic maturation of <jats:italic>P. falciparum<\/jats:italic> parasites from natural isolates. Infective merozoites were yielded which gave rise to the erythrocytic stage <jats:italic>P. falciparum<\/jats:italic> post-infection into O<jats:sup>\u2009+<\/jats:sup> erythrocytes. The full intra-hepatic maturation of the naturally isolated <jats:italic>P. falciparum<\/jats:italic> parasites in a HepG2 cell culture system is possible. This finding has important implications for malaria research and vaccine development.<\/jats:p>","DOI":"10.1371\/journal.pone.0319901","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T19:01:09Z","timestamp":1742410869000},"page":"e0319901","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evidence for infectious merozoites of Plasmodium falciparum from natural isolates of cultured hepatoma cells infected with 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