Performance of Mouse Neural Stem Cells as a Screening Reagent: Characterization of PAC1 Activity in Medium-Throughput Functional Assays

Integration of physiologically relevant in vitro assays at the earliest stages of drug discovery may improve the likelihood of successfully translating preclinical discoveries to the clinic. Assays based on in vitro-differentiated, human pluripotent stem cell (IVD hPSC)-derived cells, which may better model human physiology, are starting to impact the drug discovery process, but their implementation has been slower than originally anticipated. In this Perspective, we discuss imperatives for incorporating IVD hPSCs into drug discovery and the associated challenges.

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Primary Cells and Stem Cells in Drug Discovery: Emerging Tools for High-Throughput Screening

Eglen

Reisine²

2011

ASSAY and Drug Development Technologies

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Many drug discovery screening programs employ immortalized cells, recombinantly engineered to express a defined molecular target. Several technologies are now emerging that render it feasible to employ more physiologically, and clinically relevant, cell phenotypes. Consequently, numerous approaches use primary cells, which retain many functions seen in vivo, as well as endogenously expressing the target of interest. Furthermore, stem cells, of either embryonic or adult origin, as well as those derived from differentiated cells, are now finding a place in drug discovery. Collectively, these cells are expanding the utility of authentic human cells, either as screening tools or as therapeutics, as well as providing cells derived directly from patients. Nonetheless, the growing use of phenotypically relevant cells (including primary cells or stem cells) is not without technical difficulties, particularly when their envisioned use lies in high-throughput screening (HTS) protocols. In particular, the limited availability of homogeneous primary or stem cell populations for HTS mandates that novel technologies be developed to accelerate their adoption. These technologies include detection of responses with very few cells as well as protocols to generate cell lines in abundant, homogeneous populations. In parallel, the growing use of changes in cell phenotype as the assay readout is driving greater use of high-throughput imaging techniques in screening. Taken together, the greater availability of novel primary and stem cell phenotypes as well as new detection technologies is heralding a new era of cellular screening. This convergence offers unique opportunities to identify drug candidates for disorders at which few therapeutics are presently available.

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Performance of Mouse Neural Stem Cells as a Screening Reagent: Characterization of PAC1 Activity in Medium-Throughput Functional Assays

Cited by 3 publications

References 21 publications

Somatostatin and Neurotensin Systems in Schizophrenia

Somatostatin and Neurotensin Systems in Schizophrenia

Integrating Human Pluripotent Stem Cells into Drug Development

Primary Cells and Stem Cells in Drug Discovery: Emerging Tools for High-Throughput Screening

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