Human iPSC-Derived Hepatocyte-like Cells Support Plasmodium Liver-Stage Infection In Vitro
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Bhatia_Human iPSC.pdf
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2.36 MB
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Author(s)
Ng, Shengyong
Schwartz, Robert E.
Galstian, Ani
Gural, Nil
Shan, Jing
Prabhu, Mythili
Mota, Maria M.
Bhatia, Sangeeta N.
March-Riera, Sandra
Date Issued
February 2015
Journal
Stem Cell Reports
Publisher
Elsevier
Citation
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).
Version
Final published version
Abstract
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.
MIT Department
Harvard 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
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Creative Commons Attribution-NonCommercial-NoDerivatives
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DOI of Published Version
https://doi.org/10.1016/j.stemcr.2015.01.002
