High-Content Imaging in Disease-Relevant Cell Models
Phenotypic assays using disease-relevant cell models are an efficient approach to discover new disease drivers, perform high-throughput screens of compound or antibody libraries, understand mechanism of action, and identify clinically relevant biomarkers. At Charles River, we have developed assays to support drug discovery for specific rare diseases including ALS and Duchenne muscular dystrophy (DMD). The cell-based assays are complementary to in vivo ALS models and the MDX mouse model that is used extensively in DMD research.
Cell-Based Assays for Rare Diseases: Available Models
Patient-derived induced pluripotent stem cells (iPSC)
We work with different suppliers to access patient-derived cells for specific rare neurological diseases, including Huntington’s disease and ALS. Neural cells derived from patient tissues are used to screen therapeutic compounds, perform mechanism of action studies, and identify new disease targets.
Human embryonic stem cells (hESCs)
The pluripotency status of the ES cells is established using Oct4 staining pre- and post-differentiation. The ES cells can be differentiated into neuronal precursor cells (NPCs) and, ultimately, striatal neurons that are tested using a panel of antibody markers and/or branched DNA assays.
Rodent primary cells derived from established in vivo disease models
Disease-specific cells from the brain and other tissues are validated using morphology and functional readouts.
Cell-Based Assays for Rare Diseases: Available Methods
In addition, our scientific team performs multiple assay readouts that are applicable in human and rodent cell systems:
- High-content screening using the InCell Analyzer platform (GE)
- mRNA expression using branched DNA, qPCR, and in situ hybridization
- Protein expression changes using single molecular analysis (Quanterix), HTRF® assays, MSD® assays, Western blotting, ELISA, Luminex®, and flow cytometry/FACS
- IHC markers and histological stains with semi-quantitative image analysis and quantitative stereological analysis
- Immunocytochemistry panels to assay cell-type-specific markers
- Cell death/cell proliferation assays
Cell-Based Assays for Rare Diseases: Frequently Asked Questions (FAQs)
What are the optimal cell-based assays for phenotypic screening of novel therapies?
Cell models that recapitulate the disease-specific cell and tissue environments are ideal for phenotypic screening as they are more predictive of the in vivo therapeutic response to a compound or other modality. Cell-based assays for rare diseases are typically bespoke assays that have disease-specific endpoints.
What are the advantages of using patient-derived cell-based assays in rare disease drug discovery?
Patient-derived cells are valuable tools for screening assays as they recapitulate the true disease biology while being more cost-effective and faster than complex in vivo studies. Therefore, performing screening assays in patient-derived cell models is a good way to identify which compounds should move into animal models for in-depth efficacy and pharmacology studies.