Human embryonic stem cell-derived hepatocytes as in vitro pharmacokinetic model
An important bottle-neck in development of new drugs is the identification of compounds that suffers from negative effects. To find these compounds as early as possible is a key-challenge that will avoid unsafe and problematic pharmaceuticals to reach clinical trials, and at the end save the industry a lot of money.
One of the most important areas of drug discovery is the studies of liver metabolism of new drug candidates, an area that is today lacking a reliable cell supply for use in human in vitro test models. It is well accepted that currently used cell models have limitations such as erratic availability and variable quality. However, the access to human embryonic stem cells (hESC) has the potential to provide a safe source of high quality cells of non-limiting quantities for in vitro models in pharmaceutical research.
The aim of this PhD project is therefore to learn how hESC could mature into functional liver cells, and to arrange these cells into robust and predictive in vitro models. The PhD program will contain the following three subprojects:
- Liver-like cells will be derived from hESC, and compared to liver cells from adult liver and human liver biopsies. The presence and function of important liver-characteristics in these cells will be extensively evaluated.
- Various test systems for drug metabolism will be established. The stem cell derived liver-like cells will be explored using three different in vitro models of different grade of complexity.
- The ability of the stem cell-derived in vitro liver models to predict how new drugs will behave in humans will be evaluated.
The PhD project will ensure a lasting Nordic collaboration between the involved partners. The techniques and models developed will be unique and important for all participants. The stem cell technology in combination with the different novel models paves a new avenue of science with enormous scientific and commercial potential.