Biomaterial Database

Development of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures. 2023

Annie S P Yang, and Devanjali Dutta, and Kai Kretzschmar, and Delilah Hendriks, and Jens Puschhof, and Huili Hu, and Kim E Boonekamp, and Youri van Waardenburg, and Susana M Chuva de Sousa Lopes, and Geert-Jan van Gemert, and Johannes H W de Wilt, and Teun Bousema, and Hans Clevers, and Robert W Sauerwein

Radboud Center of Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands. annie.yang@radboudumc.nl.

Plasmodium falciparum (Pf) parasite development in liver represents the initial step of the life-cycle in the human host after a Pf-infected mosquito bite. While an attractive stage for life-cycle interruption, understanding of parasite-hepatocyte interaction is inadequate due to limitations of existing in vitro models. We explore the suitability of hepatocyte organoids (HepOrgs) for Pf-development and show that these cells permitted parasite invasion, differentiation and maturation of different Pf strains. Single-cell messenger RNA sequencing (scRNAseq) of Pf-infected HepOrg cells has identified 80 Pf-transcripts upregulated on day 5 post-infection. Transcriptional profile changes are found involving distinct metabolic pathways in hepatocytes with Scavenger Receptor B1 (SR-B1) transcripts highly upregulated. A novel functional involvement in schizont maturation is confirmed in fresh primary hepatocytes. Thus, HepOrgs provide a strong foundation for a versatile in vitro model for Pf liver-stages accommodating basic biological studies and accelerated clinical development of novel tools for malaria control.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008288	Malaria	A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.	Marsh Fever,Plasmodium Infections,Remittent Fever,Infections, Plasmodium,Paludism,Fever, Marsh,Fever, Remittent,Infection, Plasmodium,Plasmodium Infection
D009940	Organoids	An organization of cells into an organ-like structure. Organoids can be generated in culture, e.g., self-organized three-dimensional tissue structures derived from STEM CELLS (see MICROPHYSIOLOGICAL SYSTEMS). They are also found in certain NEOPLASMS.	Organoid
D010963	Plasmodium falciparum	A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics.	Plasmodium falciparums,falciparums, Plasmodium
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016778	Malaria, Falciparum	Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.	Plasmodium falciparum Malaria,Malaria, Plasmodium falciparum
D022781	Hepatocytes	The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.	Hepatic Cells,Cell, Hepatic,Cells, Hepatic,Hepatic Cell,Hepatocyte