By: Jessica McCabe,and Allan Powe, Jr., PhD.
With the number of FDA approved drugs per annum dwindling, the pharmaceutical industry is looking for new ways to increase the discovery rate of safe, clinically efficacious compounds at the very earliest stages of drug development. Currently, many of the cell lines used in early drug discovery efforts are highly engineered and often poorly reflect the native pharmacology of intended drug targets. One approach to improving this situation is to use human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) to generate various differentiated cell types of interest, e.g., dopaminergic or motor neurons. These hESC- and hiPSC-derived cells provide physiologically relevant, unadulterated in vitro cellular models that more closely reflect the biology and pharmacology of the corresponding cells in vivo. Better cellular models, could increase the probability of identifying more efficacious, safer drug candidates during hit-to-lead and lead optimization campaigns.
To help meet this need for improved, physiologically relevant cellular models, we have developed bioassays and applications for our neural and mesenchymal stem cell products with an eye toward use in drug discovery. Adhering to standards set by the pharmaceutical industry is of utmost importance in order to provide maximum utility for our drug discovery related applications. So, we look to several different websites as resources and guides in our assay development efforts. These are some of our favorites:
Assay Guidance Manual – This is the main resource we use to guide in-house assay development. The website, originally started as a collaboration between the National Chemical Genomics Center (NCGC) and Eli Lilly & Co., is now under the auspices of the National Institutes of Health Center for Translational Therapeutics (NCTT). The Assay Guidance Manual covers an extremely broad range of assays – cell based assays, enzymatic activity, receptor binding, FLIPR™ and functional assays for GPCRs and ion channels, immunoassays (including ELISAs and Westerns), RNAi screening, etc. The site also provides information on basic assay optimization and validation. Newer sections under development include in vivo assay guidelines and a section on stem cells and regenerative medicine.
LabAutopedia – This wiki-styled site was created by the Society for Laboratory Automation and Screening (SLAS) to provide a collaborative knowledgebase of the latest laboratory technology and covers topics such as laboratory automation, assay detection technologies, compound collections, genomics and proteomics, and high throughput screening. This site nicely complements the Assay Guidance Manual by providing more in-depth information on specific applications.
In addition to these sites, there are a few blogs we read regularly that help us think more broadly about stem cell assay development and to keep up-to-date on advances in the stem cell field:
SciClips – This web based, “open innovation platform” has some insightful blog entries on the utility and development of cell based assays in drug discovery. One entry along with the associated comments provides an excellent discussion of the current pros and cons of stem cell based assays as drug discovery tools.
Stem Cell Assays – Founded by William Gunn and Alexey Bersenev, this site provides not only links to protocols for newly published stem cell based methods but also casts a critical eye on stem cell research in an effort to promote increased levels of rigor in the field.
Stem Cells Portal - This site sponsored by AlphaMed Press highlights the latest news and scientific publications in stem cell research from a wide variety of journals, such as Science, Nature, and Cell, as well as those from its own press. The news feed for the Portal’s Facebook page provides a convenient, almost real-time way to keep up with newly published stem cell related articles.
We hope that you find these resources just as useful as we do in conducting your stem cell related research.