An accessible 3D HepG2/C3A liver spheroid model supporting the complete intrahepatocytic lifecycle of Plasmodium falciparum.

IF 2.4 3区 医学 Q2 PARASITOLOGY
Claire H Caygill, Salwa Omar Alqurashi, Adriana Adolfi, Jessica Carson, Angelika Sturm, Daniel S Evans, Jess B Jinks, Koen J Dechering, Lisa Reimer, Shaun H Pennington, Parveen Sharma, Stephen A Ward, Giancarlo A Biagini
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引用次数: 0

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 polarized, 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.

一个可访问的三维HepG2/C3A肝球体模型,支持恶性疟原虫的完整肝内细胞生命周期。
目前的肝期恶性疟原虫模型复杂、昂贵且很大程度上难以获得,阻碍了研究进展。在这里,我们展示了从永生化HepG2/C3A细胞生长的三维肝脏球体模型支持恶性疟原虫的完整肝内细胞生命周期。我们的研究结果表明,孢子虫感染,外红细胞形式的发展和突破感染到红细胞。3d培养的球形肝细胞在结构和功能上极化,与2D培养相比,模拟体内条件,白蛋白和尿素生成增强,关键代谢酶表达增加。这种可获取、可复制的模式降低了疟疾研究的障碍,促进了基础生物学和转化研究的进步。
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来源期刊
Parasitology
Parasitology 医学-寄生虫学
CiteScore
4.80
自引率
4.20%
发文量
280
审稿时长
3-8 weeks
期刊介绍: Parasitology is an important specialist journal covering the latest advances in the subject. It publishes original research and review papers on all aspects of parasitology and host-parasite relationships, including the latest discoveries in parasite biochemistry, molecular biology and genetics, ecology and epidemiology in the context of the biological, medical and veterinary sciences. Included in the subscription price are two special issues which contain reviews of current hot topics, one of which is the proceedings of the annual Symposia of the British Society for Parasitology, while the second, covering areas of significant topical interest, is commissioned by the editors and the editorial board.
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