Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.biomaterials.2019.05.032
Title: Hepatic spheroids used as an in vitro model to study malaria relapse
Authors: Chua, Adeline CY 
Ananthanarayanan, Abhishek
Ong, Jessica Jie Ying
Wong, Jen Yi
Yip, Andy
Singh, Nisha Hari
Qu, Yinghua 
Dembele, Laurent
McMillian, Michael 
Ubalee, Ratawan
Davidson, Silas
Tungtaeng, Anchalee
Imerbsin, Rawiwan
Gupta, Kapish 
Andolina, Chiara
Lee, Fan
Tan, Kevin S-W 
Nosten, Francois
Russell, Bruce 
Lange, Amber
Diagana, Thierry T 
Renia, Laurent 
Yeung, Bryan KS
Yu, Hanry 
Bifani, Pablo 
Keywords: Science & Technology
Technology
Engineering, Biomedical
Materials Science, Biomaterials
Engineering
Materials Science
Hepatocytes culture
Spheroids
Cellusponge
Plasmodium vivax
Plasmodium cynomolgi
Radical cure
SPOROZOITE TISSUE STAGES
CELL-DERIVED HEPATOCYTES
PLASMODIUM-VIVAX
LIVER-STAGE
PRIMATE MALARIA
HIGHLY EFFICIENT
CULTURE
ANTIMALARIAL
FALCIPARUM
PARASITES
Issue Date: 1-Sep-2019
Publisher: ELSEVIER SCI LTD
Citation: Chua, Adeline CY, Ananthanarayanan, Abhishek, Ong, Jessica Jie Ying, Wong, Jen Yi, Yip, Andy, Singh, Nisha Hari, Qu, Yinghua, Dembele, Laurent, McMillian, Michael, Ubalee, Ratawan, Davidson, Silas, Tungtaeng, Anchalee, Imerbsin, Rawiwan, Gupta, Kapish, Andolina, Chiara, Lee, Fan, Tan, Kevin S-W, Nosten, Francois, Russell, Bruce, Lange, Amber, Diagana, Thierry T, Renia, Laurent, Yeung, Bryan KS, Yu, Hanry, Bifani, Pablo (2019-09-01). Hepatic spheroids used as an in vitro model to study malaria relapse. BIOMATERIALS 216. ScholarBank@NUS Repository. https://doi.org/10.1016/j.biomaterials.2019.05.032
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.
Source Title: BIOMATERIALS
URI: https://scholarbank.nus.edu.sg/handle/10635/167515
ISSN: 01429612
18785905
DOI: 10.1016/j.biomaterials.2019.05.032
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