Research

The aim of HeMiBio is to generate a liver-simulating device (Hepatic Microfluidic Bioreactor) mimicking the structure and function of the human liver. The device should reproduce the heterotypic interactions between the parenchymal (hepatocytes) and non-parenchymal (hepatic stellate cells and hepatic sinusoidal endothelial cells) of the liver for over one month in vitro, with in vivo-like metabolic and transport function. The Hepatic Microfluidic Bioreactor could then serve to test the effects of chronic exposure to chemicals, including cosmetic ingredients, thus limiting the need for animal models.

To mimic the liver function, many increasingly more complex and clinically relevant approaches are currently used. However, these approaches are not satisfactory due to the shortage of human livers, as well as the fact that primary hepatocytes rapidly de-differentiate under standard conditions. Hence, what is needed for the cosmetics and pharmaceutical industry are innovative culture systems that incorporate hepatocytes as well as non-parenchymal liver cells, derived from expandable /renewable cell sources. HeMiBio seeks to address this unmet need using human induced pluripotent stem cells (iPSC) which offer a unique opportunity given their expected capacity to self-renew and differentiate efficiently into the desired cell type. As an alternative, the consortium will test whether cells isolated from livers can be expanded by genetic manipulation using the UpCyte® technology, without loss of mature cellular function. Finally, cocultures generated by the consortium will allow induction and maintenance of mature hepatocyte, hepatic stellate cell and hepatic sinusoidal endothelial cell function, while creating a bioreactor that can provide clinically relevant information on drug and chemical clearance and toxicity. This will allow testing of repeated dose toxicity for several weeks to ultimately months.

undifferentiated_iPSC_from_skin_fibroblasts1

 

 

 

 

 

 

 

 


Undifferentiated induced pluripotent stem cells (iPSC) from
skin fibroblasts.
Image courtesy C. Verfaillie, KULeuven.

 

HeMiBio will be tightly associated to the other consortia of the SEURAT-1 research cluster, sharing biological, technological and methodological resources, with the common objective of generating important new knowledge that can be genuinely exploited by the biotechnology, pharmaceutical and cosmetic industry in their aim to reduce the use of animals for toxicity testing.

imagesCAZE61I0backtopblue 

 

 PERTT_2