An overview of drug screening using primary and embryonic stem cells.
Cellular technologies are widely used in drug discovery to treat human diseases. Most studies involve the expression of recombinant targets in immortalized cells and measure drug interactions using simple, quantifiable responses. Such cells are also amenable to high throughput screening (HTS) methods. However, the cell phenotype employed in HTS is often determined by the assay technology available, rather than the physiological relevance of the cell background. They are, therefore, suboptimal surrogates for cells that accurately reflect human diseases. Consequently, there is growing interest in adopting primary and embryonic stem cells in drug discovery. Primary cells are already used in secondary screening assays in conjunction with confocal imaging techniques, as well as in target validation studies employing, for example, gene silencing approaches. Stem cells can be grown in unlimited quantities and can be derived from transgenic animals engineered to express disease causing proteins better coupling the molecular target with function in vivo. Human stem cells also offer unique opportunities for drug discovery in that they can be directed to specific phenotypes thus providing a framework to identify tissue-selective agents. Organizing stem cells into networks resembling those in native tissues, potentially returns drug discovery back to the highly successful pharmacological methods of the past, in which organ and tissue based systems were used, but with the advantage that they can be utilized using modern HTS technologies. This emerging area will lead to discovery of compounds whose effect in vivo is more predictable thereby increasing the efficiency of drugs that ameliorate human disease.
Eglen
Richard M
RM
Bio-Discovery, PerkinElmer Life and Analytical Sciences, Waltham, MA 02451-1457, USA. richard.eglen@perkinelmer.com
Gilchrist
Annette
A
Reisine
Terry
T
D000818:Animals; D001681:Biological Assay / Q000379:methods*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans