title: A microscale human liver platform that supports the hepatic stages of Plasmodium falciparum and 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.
authors.affiliation: Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: March
authors.forename: Shengyong
authors.initials: S
authors.lastname: Ng
authors.forename: Soundarapandian
authors.initials: S
authors.lastname: Velmurugan
authors.forename: Ani
authors.initials: A
authors.lastname: Galstian
authors.forename: Jing
authors.initials: J
authors.lastname: Shan
authors.forename: David J
authors.initials: DJ
authors.lastname: Logan
authors.forename: Anne E
authors.initials: AE
authors.lastname: Carpenter
authors.forename: David
authors.initials: D
authors.lastname: Thomas
authors.forename: B Kim Lee
authors.initials: BK
authors.lastname: Sim
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
authors.forename: Sangeeta N
authors.initials: SN
authors.lastname: Bhatia
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D022781:Hepatocytes / Q000166:cytology / Q000469:parasitology*; D006801:Humans; D008018:Life Cycle Stages; D008099:Liver / Q000166:cytology* / Q000469:parasitology; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology*; D010274:Parasitology / Q000379:methods*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development*; D010966:Plasmodium vivax / Q000187:drug effects / Q000254:growth & development*
chemical_list: D000962:Antimalarials