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Stem Cell Reports. 2015 Mar 10;4(3):348-59. doi: 10.1016/j.stemcr.2015.01.002. Epub 2015 Feb 7.

Human iPSC-derived hepatocyte-like cells support Plasmodium liver-stage infection in vitro.

Author information

1
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
2
Health Sciences and Technology/Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
3
Health Sciences and Technology/Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute, Cambridge, MA 02139, USA.
4
Health Sciences and Technology/Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
5
Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, 1649-028 Lisboa, Portugal; Howard Hughes Medical Institute, Koch Institute, and Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
6
Health Sciences and Technology/Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Koch Institute, and Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute, Cambridge, MA 02139, USA. Electronic address: sbhatia@mit.edu.

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.

PMID:
25660406
PMCID:
PMC4375936
DOI:
10.1016/j.stemcr.2015.01.002
[Indexed for MEDLINE]
Free PMC Article

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