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bioRxiv · 10.1101/2024.11.06.621813

An Accessible 3D HepG2/C3A Liver Spheroid Model Supporting the Complete Intrahepatocytic Lifecycle of Plasmodium falciparum

Alqurashi, S. O.·Caygill, C. H.·Adolfi, A.·Carson, J.·Sturm, A.·Dechering, K. J.·Reimer, L.·Pennington, S. H.·Sharma, P.·Ward, S. A.·Biagini, G.
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Abstract

Current liver-stage Plasmodium falciparum 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 P. falciparum. Our results demonstrate sporozoite infection, development of exoerythrocytic forms, and breakthrough infection into erythrocytes. The 3D-grown spheroid hepatocytes are structurally and functionally polarised, displaying enhanced albumin and urea production and increased expression of key metabolic enzymes, mimicking in vivo conditions - relative to 2D cultures. This accessible, reproducible model lowers barriers to malaria research, promoting advancements in fundamental biology and translational research.

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Alqurashi, S. O., Caygill, C. H., Adolfi, A., Carson, J., Sturm, A., Dechering, K. J., Reimer, L., Pennington, S. H., Sharma, P., Ward, S. A., Biagini, G.. 2024-11-06. An Accessible 3D HepG2/C3A Liver Spheroid Model Supporting the Complete Intrahepatocytic Lifecycle of Plasmodium falciparum. https://doi.org/10.1101/2024.11.06.621813

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