Engineering in vitro models of hepatofibrogenesis

Adv Drug Deliv Rev. 2017 Nov 1;121:147-157. doi: 10.1016/j.addr.2017.05.018. Epub 2017 May 31.

Abstract

Chronic liver disease is a major cause of morbidity and mortality worldwide marked by chronic inflammation and fibrosis/scarring, resulting in end-stage liver disease and its complications. Hepatic stellate cells (HSCs) are a dominant contributor to liver fibrosis by producing excessive extracellular matrix (ECM), irrespective of the underlying disease aetiologies, and for many decades research has focused on the development of a number of anti-fibrotic strategies targeting this cell. Despite major improvements in two-dimensional systems (2D) by using a variety of cell culture models of different complexity, an efficient anti-fibrogenic therapy has yet to be developed. The development of well-defined three-dimensional (3D) in vitro models, which mimic ECM structures as found in vivo, have demonstrated the importance of cell-matrix bio-mechanics, the complex interactions between HSCs and hepatocytes and other non-parenchymal cells, and this to improve and promote liver cell-specific functions. Henceforth, refinement of these 3D in vitro models, which reproduce the liver microenvironment, will lead to new objectives and to a possible new era in the search for antifibrogenic compounds.

Keywords: 2 dimensional system (2D); 3 dimensional system (3D); Cell sheet stacking; Decellularised liver scaffolds; Extracellular matrix (ECM); Hepatic stellate cells (HSCs); Liver fibrosis; Matrigel/hydrogel; Organoids/spheroids; Precision-Cut Liver Slices (PCLS).

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques*
  • Drug Discovery
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / pathology
  • Hepatic Stellate Cells / drug effects
  • Hepatic Stellate Cells / metabolism*
  • Hepatic Stellate Cells / pathology*
  • Humans
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology*
  • Models, Biological*
  • Tissue Engineering*
  • Translational Medical Research