An accessible 3D HepG2/C3A liver spheroid model supporting the complete intrahepatocytic lifecycle of <i>Plasmodium falciparum</i>
Current liver-stage <i>Plasmodium falciparum</i> 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 <i>P. falciparum</i>. Our results demonstrate sporozoite infection, development of exoerythrocytic forms and breakthrough infection into erythrocytes. The 3D-grown spheroid hepatocytes are structurally and functionally polarized, displaying enhanced albumin and urea production and increased expression of key metabolic enzymes, mimicking <i>in vivo</i> conditions - relative to 2D cultures. This accessible, reproducible model lowers barriers to malaria research, promoting advancements in fundamental biology and translational research.
Authors
- Koen J. Dechering (ORCID: https://orcid.org/0000-0002-8124-4634)
- Jessica Jinks (ORCID: https://orcid.org/0000-0002-8711-0290)
- Adriana Adolfi (ORCID: https://orcid.org/0000-0003-0573-5076)
- Angelika Sturm (ORCID: https://orcid.org/0000-0003-0051-6800)
- Lisa J. Reimer (ORCID: https://orcid.org/0000-0002-9711-4981)
- Parveen Sharma (ORCID: https://orcid.org/0000-0002-5534-2417)
- Giancarlo A. Biagini (ORCID: https://orcid.org/0000-0001-6356-6595)
- Jessica Carson
- Shaun H. Pennington (ORCID: https://orcid.org/0000-0002-7160-6275)
- Stephen A. Ward (ORCID: https://orcid.org/0000-0003-2331-3192)
- Daniel S. Evans (ORCID: https://orcid.org/0000-0003-4185-7687)
- Claire H Caygill (ORCID: https://orcid.org/0000-0002-5546-9346)
- Salwa Omar Alqurashi
Institutions
- University of Liverpool (GB)
- Liverpool School of Tropical Medicine (GB)
- Merseytravel (GB)
- TropIQ Health Sciences (NL)
Publication Details
- Journal
- Parasitology
- Published
- 2025-06-20
- DOI
- https://doi.org/10.1017/s0031182025100322
- Citations
- 1
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 1.88