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

Cell Host Microbe
Authors
Keywords
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.

Year of Publication
2013
Journal
Cell Host Microbe
Volume
14
Issue
1
Pages
104-15
Date Published
2013 Jul 17
ISSN
1934-6069
URL
DOI
10.1016/j.chom.2013.06.005
PubMed ID
23870318
PubMed Central ID
PMC3780791
Links
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