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Microphysiological systems meet hiPSC technology - New tools for disease modeling of liver infections in basic research and drug development

Journal

ADVANCED DRUG DELIVERY REVIEWS
Volume 140, Issue -, Pages 51-67

Publisher

ELSEVIER
DOI: 10.1016/j.addr.2018.06.008

Keywords

Hepatocyte like cells (HLC); Viral liver infections; Malaria; Inflammation; Stem cells; iPSC differentiation; Immune response; Drug screening

Funding

  1. Federal Ministry of Education and Research [01EK1612B, 01EO1002]
  2. German Research Foundation [MO 2968/1-1, SFB 1278]
  3. German Federal Institute for Risk Assessment [1328-511]
  4. German Research Platform for Zoonoses [01KI1109]
  5. Federal Construction Bank Thiwingia [2011 VF 0005]
  6. Center for Sepsis Control and Care, Jena [G4.3]

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Complex cell culture models such as microphysiological models (MPS) mimicking human liver functionality in vitro are in the spotlight as alternative to conventional cell culture and animal models. Promising techniques like microfluidic cell culture or micropatterning by 3D bioprinting are gaining increasing importance for the development of MPS to address the needs for more predictivity and cost efficiency. In this context, human induced pluripotent stem cells (hiPSCs) offer new perspectives for the development of advanced liver-on-chip systems by recreating an in vivo like microenvironment that supports the reliable differentiation of hiPSCs to hepatocyte-like cells (HLC). In this review we will summarize current protocols of HLC generation and highlight recently established MPS suitable to resemble physiological hepatocyte function in vitro. In addition, we are discussing potential applications of liver MPS for disease modeling related to systemic or direct liver infections and the use of MPS in testing of new drug candidates. (C) 2018 The Authors. Published by Elsevier B.V.

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