Hepatic spheroids used as an in vitro model to study malaria relapse
© 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 hypnoz...
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th-mahidol.501022020-01-27T16:07:28Z Hepatic spheroids used as an in vitro model to study malaria relapse 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 Biochemistry, Genetics and Molecular Biology Chemical Engineering Engineering Materials Science © 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. 2020-01-27T07:40:16Z 2020-01-27T07:40:16Z 2019-09-01 Article Biomaterials. Vol.216, (2019) 10.1016/j.biomaterials.2019.05.032 18785905 01429612 2-s2.0-85066946860 https://repository.li.mahidol.ac.th/handle/123456789/50102 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85066946860&origin=inward |
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Biochemistry, Genetics and Molecular Biology Chemical Engineering Engineering Materials Science 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 |
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© 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. |
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A-Star, Singapore Immunology Network |
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A-Star, Singapore Immunology Network 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 |
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Article |
author |
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 |
author_sort |
Adeline C.Y. Chua |
title |
Hepatic spheroids used as an in vitro model to study malaria relapse |
title_short |
Hepatic spheroids used as an in vitro model to study malaria relapse |
title_full |
Hepatic spheroids used as an in vitro model to study malaria relapse |
title_fullStr |
Hepatic spheroids used as an in vitro model to study malaria relapse |
title_full_unstemmed |
Hepatic spheroids used as an in vitro model to study malaria relapse |
title_sort |
hepatic spheroids used as an in vitro model to study malaria relapse |
publishDate |
2020 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/50102 |
_version_ |
1763494513662230528 |