ArticleMalaria journal2024
Human liver organoids are susceptible to Plasmodium vivax infection.
Article in Malaria journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- A bivalent multi-epitope vaccine targeting CSP and TRAP of Plasmodium vivax designed through immunoinformatics and structural bioinformatics.BMC microbiology · 2026Article
- Beyond the mouse: organoids, spheroids, and organs-on-chips as the (inevitable) future of malaria research?Malaria journal · 2026Review
- Small is big: growing impact of small molecule mass spectrometry in infectious disease drug development.mSphere · 2026Review
- Organoid-based systems for biomedical innovation: advances in disease modeling, drug screening, and precision medicine.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Human organoids and organ-on-chip systems for AI-guided therapeutic discovery against emerging and re-emerging infections.Frontiers in pharmacology · 2026Review
- Simian iPS-derived hepatocytes supportFrontiers in cellular and infection microbiology · 2026Article
- Development of a High-Throughput Screening Platform and a Pathogenesis Model forInternational journal of molecular sciences · 2025Article
- Experimental models of liver-stage malaria: Progress, gaps, and challenges.PLoS pathogens · 2025Review
- Correction: Human liver organoids are susceptible to Plasmodium vivax infection.Malaria journal · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe eradication of Plasmodium vivax malaria is complicated due to the presence of hypnozoites, the hidden dormant form of the parasite that is present in the liver. 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.
methodsOrganoids 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 Plasmodium vivax 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.
resultsGenerated liver organoids showed upregulation of liver specific transcripts including hepatic nuclear factor 4A (HNF4A), alpha-fetoprotein (AFP), and albumin (ALB) 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 P. vivax sporozoites, PvUIS4 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.
conclusionsStem cell-derived liver organoids resemble mature liver cells in terms of liver functions and are susceptible to infection with P. vivax sporozoites, paving the way for studies on the mechanism of hypnozoite formation and testing of possible hypnozoitocidal drugs.
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