Micropatterned Coculture of Primary Human Hepatocytes and Supportive Cells for the Study of Hepatotropic Pathogens

Overview

Journal Nat Protoc

Specialties Biology
Pathology
Science

Date 2015 Nov 20

PMID 26584444

Citations 71

Authors

Sandra March

Vyas Ramanan

Kartik Trehan

Shengyong Ng

Ani Galstian

Nil Gural

Margaret A Scull

Amir Shlomai

Maria M Mota

Heather E Fleming

Salman R Khetani

Charles M Rice

Sangeeta N Bhatia

Affiliations

Soon will be listed here.

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.

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