Expected Outcome

  • HeMiBio will significantly decrease the need for the pharmaceutical industry to use primary animal derived cells for a number of aspects of ADME/Tox studies, and hence REDUCE significantly the need for animals in experimentation as it will allow REPLACEMENT of animal derived liver cells by in vitro generated liver cells.
  • Hepatocytes being the predominant target of HBV and HCV infections (hepatitis B & C viruses), HeMiBio may alleviate the problem of paucity of human hepatocytes to use in vitro to evaluate the infection process, the influence of hepatitis viruses on cell function, and identify additional targets for drug development.
  • HeMiBio liver-simulating device will allow the evaluation of antifibrotic drugs: the generation of a renewable source of hepatic stellate cells from hiPSC should make the investigation of possible novel antifibrotic agents more feasible.
  • The hepatocytes generated within HeMiBio could be used in Bio-Artificial Liver (BAL) systems. A BAL device is an artificial extracorporeal supportive device for individuals suffering from acute liver failure that replaces all failing liver functions of the diseased liver, including removal of toxins, thus yielding improved survival. The current systems under development use cell lines that do not show all required liver cell functions. The availability of non-transformed human hepatocytes, whether derived from liver tissue or stem cells would alleviate such problems.
  • Translation of HeMiBio results to other organ-simulating devices: the technology developed in HeMiBio, i.e. cells that are manipulated as such that their differentiation state, functionality and viability can be monitored and the inclusion of sensors that can monitor the environment of the cells, can be translated to other organ systems for high-throughput screening for the effect of drug candidates without needing animals.

stelate_cells_1

 

 

 

 

Activated hepatic stellate cell (Myosin IIA in green, Beta-actin in red, nucleus in blue). Image courtesy L. van Grunsven, VUB