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|Title:||Hepatic spheroids used as an in vitro model to study malaria relapse|
|Authors:||Adeline C.Y. Chua|
Jessica Jie Ying Ong
Jen Yi Wong
Nisha Hari Singh
Kevin S-W Tan
Thierry T. Diagana
Bryan K.S. Yeung
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
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|
|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.|
|Appears in Collections:||Scopus 2019|
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