Human iPSC-Derived Hepatocyte-like Cells Support Plasmodium Liver-Stage Infection In?Vitro

摘要

Malaria eradication is a major goal in public health but is challenged by relapsing malaria species, expanding drug resistance, and theinfluence of host genetics on antimalarial drug efficacy. To overcome these hurdles, it is imperative to establish in vitro assays of liverstagemalaria for drug testing. Induced pluripotent stem cells (iPSC) potentially allow the assessment of donor-specific drug responses,and iPSC-derived hepatocyte-like cells (iHLCs) can facilitate the study of host genetics on host-pathogen interactions and the discoveryof novel targets for antimalarial drug development.We establish in vitro liver-stage malaria infections in iHLCs using P. berghei, P. yoelii,P. falciparum, and P. vivax and show that differentiating cells acquire permissiveness to malaria infection at the hepatoblast stage.We alsocharacterize antimalarial drug metabolism capabilities of iHLCs using prototypical antimalarial drugs and demonstrate that chemicalmaturation of iHLCs can improve their potential for antimalarial drug testing applications.