Human embryonic stem cell technologies and drug discovery.
Development of new drugs is costly and takes huge resources into consideration. The big pharmaceutical companies are currently facing increasing developmental costs and a lower success-rate of bringing new compounds to the market. Therefore, it is now of outmost importance that the drug-hunting companies minimize late attritions due to sub-optimal pharmacokinetic properties or unexpected toxicity when entering the clinical programs. To achieve this, a strong need to test new candidate drugs in assays of high human relevance in vitro as early as possible has been identified. The traditionally used cell systems are however remarkably limited in this sense, and new improved technologies are of greatest importance. The human embryonic stem cells (hESC) is one of the most powerful cell types known. They have not only the possibility to divide indefinitely; these cells can also differentiate into all mature cell types of the human body. This makes them potentially very valuable for pharmaceutical development, spanning from use as tools in early target studies, DMPK or safety assessment, as screening models to find new chemical entities modulating adult stem cell fate, or as the direct use in cell therapies. This review illustrates the use of hESC in the drug discovery process, today, as well as in a future perspective. This will specifically be exemplified with the most important cell type for pharmaceutical development-the hepatocyte. We discuss how hESC-derived hepatocyte-like cells could improve this process, and how these cells should be cultured if optimized functionality and usefulness should be achieved. J. Cell. Physiol. 219: 513-519, 2009. (c) 2009 Wiley-Liss, Inc.
Jensen
Janne
J
Cellartis AB, Göteborg, Sweden.
Hyllner
Johan
J
Björquist
Petter
P
D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods / Q000639:trends; D002454:Cell Differentiation; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects