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Harnessing Stem Cells for Drug Discovery: Part 2

How are stem cells advancing compound screening and analysis of drug-like properties?

Stem cells are emerging as significant reagents in drug development pipelines. In part 1 of this series, we discussed how advances in stem cell culture and differentiation are providing high quality and quantity human cells and cell lines. Here we discuss how these cells are advantageous for drug development platforms.

Advancing compound screening platforms

Stem cells provide diverse reagents to investigate potential therapeutics.1 Induced pluripotent stem cells (iPSCs) can be derived into a plethora of cellular subtypes. The cells can be derived from patients with distinct pathogenic genetic lesions establishing a platform to directly address how the lesion behaves in response to potential therapeutics. The variety of cell types available for screening extends research capabilities. For example, cancer stem cells can also be expanded to be used in screening platforms. Interestingly, stem cells and their features are amenable to 3D culturing techniques, which offers many advantages for drug development screening. The genetic and tissue diversity available through iPSC techniques seems limitless. The use of specific cell types, cells derived with specific genetic lesions, and importantly human cells enables the identification of better therapeutic candidates. Several Scientist vendors provide custom services with unique cell line development and assay development services.

Stem cells can be used to determine drug-like properties.
Image credit: Nature Chemical Biology 6, 476 – 479 (2010) doi:10.1038/nchembio.394

Predicting in vivo toxicity and drug-like properties of lead molecules

As new drug candidates are identified, lead molecules must be honed for the appropriate properties that will allow them to be used in humans. These include toxicity, stability, absorption, etc (Figure 1). Stem cell screening platforms are now available to characterize the properties of compounds prior to introduction into in vivo models.1 Cardiotoxicity is a major concern for new compounds. GE Healthcare has developed a predictive model for assessing cardiotoxicity. Human embryonic stem cells have been derived into cardiomyocytes and produced in large quantities with high quality standards. These cells can be used for eliminating compounds that might have cardiotoxic effects. Importantly, cellular hallmarks of toxicity can be monitored including nuclear morphology, mitochondrial health and calcium levels creating rapid and convenient assessment criteria for monitoring the assays. This can be used in conjunction with high content imaging systems to monitor cellular responses quickly and efficiently. Scientist vendors offer high content imaging services to support your research.

The use of stem cells in compound and toxicity screening platforms provides useful tools in creating better therapeutics faster and circumventing expensive failures in the clinic. In the next blog of this series, we discuss how stem cells are advancing our understanding of disease mechanisms.

  1. Cromley, J. Stem cells rapidly gaining traction in research and drug discovery. Drug Discovery World. Summer 2013.