Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens.

Nat Protoc
Authors
Keywords
Abstract

The development of therapies and vaccines for human hepatropic pathogens requires robust model systems that enable the study of host-pathogen interactions. However, in vitro liver models of infection typically use either hepatoma cell lines that exhibit aberrant physiology or primary human hepatocytes in culture conditions in which they rapidly lose their hepatic phenotype. To achieve stable and robust in vitro primary human hepatocyte models, we developed micropatterned cocultures (MPCCs), which consist of primary human hepatocytes organized into 2D islands that are surrounded by supportive fibroblast cells. By using this system, which can be established over a period of days, and maintained over multiple weeks, we demonstrate how to recapitulate in vitro hepatic life cycles for the hepatitis B and C viruses and the Plasmodium pathogens P. falciparum and P. vivax. The MPCC platform can be used to uncover aspects of host-pathogen interactions, and it has the potential to be used for drug and vaccine development.

Year of Publication
2015
Journal
Nat Protoc
Volume
10
Issue
12
Pages
2027-53
Date Published
2015 Dec
ISSN
1750-2799
URL
DOI
10.1038/nprot.2015.128
PubMed ID
26584444
Links
Grant list
R01 DK85713 / DK / NIDDK NIH HHS / United States
Howard Hughes Medical Institute / United States