Publication:
Hepatic spheroids used as an in vitro model to study malaria relapse

3

Issued Date

2019-09-01

Resource Type

Article

ISSN

18785905
01429612

DOI

10.1016/j.biomaterials.2019.05.032

Other identifier(s)

2-s2.0-85066946860

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Biomaterials. Vol.216, (2019)

Suggested Citation

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 Hepatic spheroids used as an in vitro model to study malaria relapse. Biomaterials. Vol.216, (2019). doi:10.1016/j.biomaterials.2019.05.032 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/50102

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Title

Hepatic spheroids used as an in vitro model to study malaria relapse

Author(s)

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

Other Contributor(s)

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

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.

Keyword(s)

Biochemistry, Genetics and Molecular Biology
 Chemical Engineering
 Engineering
 Materials Science

Availability

URI

https://repository.li.mahidol.ac.th/handle/123456789/50102

Collections

Scopus 2019