Human iPSC-Derived Hepatocyte-like Cells Support Plasmodium Liver-Stage Infection In Vitro
Author(s)Ng, Shengyong; Schwartz, Robert E.; Galstian, Ani; Gural, Nil; Shan, Jing; Prabhu, Mythili; Mota, Maria M.; Bhatia, Sangeeta N.; March-Riera, Sandra; ... Show more Show less
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Malaria eradication is a major goal in public health but is challenged by relapsing malaria species, expanding drug resistance, and the influence of host genetics on antimalarial drug efficacy. To overcome these hurdles, it is imperative to establish in vitro assays of liver-stage malaria 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 discovery of 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 also characterize antimalarial drug metabolism capabilities of iHLCs using prototypical antimalarial drugs and demonstrate that chemical maturation of iHLCs can improve their potential for antimalarial drug testing applications.
DepartmentHarvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science; Koch Institute for Integrative Cancer Research at MIT
Stem Cell Reports
Ng, Shengyong, Robert E. Schwartz, Sandra March, Ani Galstian, Nil Gural, Jing Shan, Mythili Prabhu, Maria M. Mota, and Sangeeta N. Bhatia. “Human iPSC-Derived Hepatocyte-Like Cells Support Plasmodium Liver-Stage Infection In Vitro.” Stem Cell Reports (February 2015).
Final published version