3D liver models in tissue engineering and toxicology

In her thesis, Viktoriia Starokozhko developed new and improved existing liver models for the use in tissue engineering and toxicology. One of the models she described and used are liver slices (PCLS), a mini-organ model for the liver. PCLS are used already for many years in various fields of pharmacology and toxicology. However, their application is limited by their short life span. In this thesis it was shown that viability and functionality of PCLS can be prolonged to 5 days by using enriched media, which will allow performance of subchronic toxicity studies. The application of PCLS in toxicology studies was successfully demonstrated for drug-induced cholestasis.Another topic described in this thesis is a liver-on-a-chip or bioartificial liver (BAL). To date, the only effective treatment available for patients with acute liver failure is liver transplantation. However, orthotopic transplantation is limited by the shortage of liver donors. Therefore, creation of a BAL has been proposed as an alternative approach to whole liver transplantation, or as a temporary solution, reducing the mortality rate of patients on the waiting list. In this thesis, the challenges on the road to the development of such a BAL are described. Moreover, a prototype of an extracorporeal BAL device is presented based on human induced pluripotent stem cells, which considered to be the most promising source for the generation of human liver cells. Fully functional liver cells were derived from these stem cells, which is a major step forward in liver tissue engineering. The application of these human liver models significantly reduces the use of animals and improves prediction of toxicity for man