Cell-based Assay Formats
Over the years, we have developed and implemented numerous cell-based assay formats either for our own use, or at the request of partners. Such assays, of differing levels of sophistication and throughput, have been used for compound library screens, the de novo identification of novel factors/cell modulators, as well as for characterizing and defining the utility of our own therapeutic products. The implementation of high content analysis (HCA) with the In Cell Analyzer 2000 is a powerful new enhancement to our cell-based assay toolbox, as we continue to expand our offerings and introduce additional applications for our proprietary cells, such as the use of hLEC™ human liver engrafting cells for ADMETox.
Examples of cell-based assays formats developed and applied to date include:
- Proliferation — Screening for activators or inhibitors of cell proliferation
- Self-renewal — Defining the “stemness” of a cell and the effects of modulators thereon
- Differentiation — High content analysis for modulators of cell fate
- Function — Defining and characterizing the correct functioning of stem cells, progenitor cells and differentiated cells
In Vivo Assays
A key enabling tool for advancing our own cell-based therapeutics towards the clinic has been the establishment of representative in vivo models of disease with which to study the engraftment, migration, differentiation and function of human cells transplanted into immuno-deficient rodents. Such models include:
- Neurodegeneration in brain
- Spinal cord injury
- Retinal degeneration
- Myelin deficiency
Such models can be used to validate lead candidates for pharmaceutical and biotechnology partners and provide direct insight into the potential toxicology and/or efficacy of a compound in different in vivo modalities in the actual disease setting.
- Human cells transplanted directly into the rodent
- Human cells transplanted and then differentiated in the rodent
- Pre-treated human cells that are then transplanted into the rodent
Such studies can also be a direct consideration relative to the 3Rs1 approach of Addendum to ICH S6: “Preclinical Safety Evaluation of Biotechnology-derived Pharmaceuticals” in terms of alternative methods that reduce, refine, and replace (3Rs) the use of animals for testing.