title: Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens.
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.
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: March
authors.affiliation: Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Vyas
authors.initials: V
authors.lastname: Ramanan
authors.affiliation: Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Kartik
authors.initials: K
authors.lastname: Trehan
authors.affiliation: Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Shengyong
authors.initials: S
authors.lastname: Ng
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Ani
authors.initials: A
authors.lastname: Galstian
authors.affiliation: Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Nil
authors.initials: N
authors.lastname: Gural
authors.affiliation: Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, New York, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Scull
authors.affiliation: Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, New York, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Shlomai
authors.affiliation: Unidade de Malaria, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Mota
authors.affiliation: Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Heather E
authors.initials: HE
authors.lastname: Fleming
authors.affiliation: Department of Mechanical Engineering, School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado, USA.
authors.forename: Salman R
authors.initials: SR
authors.lastname: Khetani
authors.affiliation: Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, New York, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Howard Hughes Medical Institute, Cambridge, Massachusetts, USA.|Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Sangeeta N
authors.initials: SN
authors.lastname: Bhatia
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods*; D005347:Fibroblasts / Q000166:cytology; D016174:Hepacivirus / Q000502:physiology*; D006509:Hepatitis B / Q000378:metabolism; D006515:Hepatitis B virus / Q000502:physiology*; D006526:Hepatitis C / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000469:parasitology* / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008288:Malaria / Q000378:metabolism; D051379:Mice; D010961:Plasmodium / Q000502:physiology*; D010963:Plasmodium falciparum / Q000502:physiology; D010966:Plasmodium vivax / Q000502:physiology; D046888:Tissue Array Analysis / Q000379:methods