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Title: Hepatic spheroids used as an in vitro model to study malaria relapse
Authors: Adeline C.Y. Chua
Abhishek Ananthanarayanan
Jessica Jie Ying Ong
Jen Yi Wong
Andy Yip
Nisha Hari Singh
Yinghua Qu
Laurent Dembele
Michael McMillian
Ratawan Ubalee
Silas Davidson
Anchalee Tungtaeng
Rawiwan Imerbsin
Kapish Gupta
Chiara Andolina
Fan Lee
Kevin S-W Tan
François Nosten
Bruce Russell
Amber Lange
Thierry T. Diagana
Laurent Rénia
Bryan K.S. Yeung
Hanry Yu
Pablo Bifani
A-Star, Singapore Immunology Network
Mechanobiology Institute, Singapore
Yong Loo Lin School of Medicine
A-Star, Institute of Bioengineering and Nanotechnology
Novartis Institute for Tropical Diseases Pte. Ltd.
University of Otago
Armed Forces Research Institute of Medical Sciences, Thailand
Mahidol University
Nuffield Department of Clinical Medicine
Novartis Institutes for BioMedical Research, Inc.
Invitrocue Pte Ltd. 138667
Université des Sciences
Keywords: Biochemistry, Genetics and Molecular Biology;Chemical Engineering;Engineering;Materials Science
Issue Date: 1-Sep-2019
Citation: Biomaterials. Vol.216, (2019)
Abstract: © 2019 The Authors Hypnozoites are the liver stage non-dividing form of the malaria parasite that are responsible for relapse and acts as a natural reservoir for human malaria Plasmodium vivax and P. ovale as well as a phylogenetically related simian malaria P. cynomolgi. Our understanding of hypnozoite biology remains limited due to the technical challenge of requiring the use of primary hepatocytes and the lack of robust and predictive in vitro models. In this study, we developed a malaria liver stage model using 3D spheroid-cultured primary hepatocytes. The infection of primary hepatocytes in suspension led to increased infectivity of both P. cynomolgi and P. vivax infections. We demonstrated that this hepatic spheroid model was capable of maintaining long term viability, hepatocyte specific functions and cell polarity which enhanced permissiveness and thus, permitting for the complete development of both P. cynomolgi and P. vivax liver stage parasites in the infected spheroids. The model described here was able to capture the full liver stage cycle starting with sporozoites and ending in the release of hepatic merozoites capable of invading simian erythrocytes in vitro. Finally, we showed that this system can be used for compound screening to discriminate between causal prophylactic and cidal antimalarials activity in vitro for relapsing malaria.
ISSN: 18785905
Appears in Collections:Scopus 2019

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