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Cell Host Microbe DOI:10.1016/j.chom.2013.06.005

A microscale human liver platform that supports the hepatic stages of Plasmodium falciparum and vivax.

Publication TypeJournal Article
Year of Publication2013
AuthorsMarch, S, Ng, S, Velmurugan, S, Galstian, A, Shan, J, Logan, DJ, Carpenter, AE, Thomas, D, B Sim, KLee, Mota, MM, Hoffman, SL, Bhatia, SN
JournalCell Host Microbe
Volume14
Issue1
Pages104-15
Date Published2013 Jul 17
ISSN1934-6069
KeywordsAnimals, Antimalarials, Cells, Cultured, Drug Evaluation, Preclinical, Hepatocytes, Humans, Life Cycle Stages, Liver, Malaria, Parasitology, Plasmodium falciparum, Plasmodium vivax
Abstract

The Plasmodium liver stage is an attractive target for the development of antimalarial drugs and vaccines, as it provides an opportunity to interrupt the life cycle of the parasite at a critical early stage. However, targeting the liver stage has been difficult. Undoubtedly, a major barrier has been the lack of robust, reliable, and reproducible in vitro liver-stage cultures. Here, we establish the liver stages for both Plasmodium falciparum and Plasmodium vivax in a microscale human liver platform composed of cryopreserved, micropatterned human primary hepatocytes surrounded by supportive stromal cells. Using this system, we have successfully recapitulated the full liver stage of P. falciparum, including the release of infected merozoites and infection of overlaid erythrocytes, as well as the establishment of small forms in late liver stages of P. vivax. Finally, we validate the potential of this platform as a tool for medium-throughput antimalarial drug screening and vaccine development.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S1931-3128(13)00221-7
DOI10.1016/j.chom.2013.06.005
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23870318?dopt=Abstract

Alternate JournalCell Host Microbe
PubMed ID23870318
PubMed Central IDPMC3780791
Grant List / / Howard Hughes Medical Institute / United States
P30 CA014051 / CA / NCI NIH HHS / United States
R01 GM089652 / GM / NIGMS NIH HHS / United States
R01GM089652 / GM / NIGMS NIH HHS / United States