Recellularization of decellularized rad liver with human hepatic cells as a novel 3D culture model for pharmaco-toxicological research (FWOAL643)

The liver, and in particular the hepatocyte, plays a key role in the occurrence of drug-induced liver damage. Hence, primary hepatocyte cultures are currently the gold standard in vitro tool to investigate potential adverse effects of candidate pharmaceuticals in the early phases of drug development. However, because of the progressive loss of their specific in vivo hepatic properties during standard 2D culture, primary hepatocyte cultures can at present only be used for short-term studies.
Attempts to overcome this dedifferentiation by mimicking in vitro the natural blood components and flow, the extracellular matrix backbone and multicellular cooperation of the hepatocytes, have, however, only been partially successful. Therefore, in the current project, a novel and unique naturally derived rat liver scaffold will be used as a tool in the bio-engineering of a more sophisticated, ex vivo 3D system for preclinical drug development. Rat livers will be decellularized and subsequently recellularized with human hepatocytes in order to create a 3D ex vivo humanized model aimed at testing lead pharmaceutical compounds before entering the clinical development phase.
This unique liver scaffold will also be explored as a natural environment to differentiate human liver progenitors into hepatic cells.

Keywords:Cultures And Co-Cultures, Apoptosis, apoptosis, Hepatocytes, Cosmetics, Isobutene, Toxicity, Saponins, Dermato-Cosmetics, Anti-Epileptic Drugs, Phytochemistry, Dermato-Cosmetic Sciences, Drug Metabolism, In Vitro Toxicology, Liver Cells, Pharmacognosy, Human Skin, Keratinocytes

Disciplines:Basic sciences, Pharmaceutical sciences