Evaluation of human skin-derived precursor cells and their in vitro generated hepatic derivatives in experimental liver disease mouse models.

Drug-induced liver injury (DILI) is an important cause of liver failure which can be either acute or chronic. Currently, orthotopic liver transplantation (OLT) is the primary choice of treatment for life-threatening liver diseases. However, OLT as well as allogeneic human hepatocyte transplantation are hampered by the shortage of human organ donor material. Therefore, other sources such as human stem cells, displaying the ability for self-renewal and potential for multi-lineage differentiation, are being explored and studied in animal-based liver disease models. Here, human skin-derived precursors (hSKPs) are studied. This particular stem cell population (i) can be isolated from both autogeneic and allogeneic postnatal human skin, (ii) differentiates in vitro into hepatocyte-like cells and (iii) exhibits favorable immunological properties, making them potentially interesting for drug screening purposes and for later allogeneic therapeutical applications. In the actually running postdoctoral research project, their impact on liver disease will be explored in suitable liver disease mouse models. In vivo engraftment of the cells and their functionality upon different stages of hepatic differentiation will be carefully assessed in terms of xenobiotic biotransformation, drug transporter capacity and other vital functions. Also their immunogenicity will be defined as this could provide key information with respect to allogeneic rejection.