Cell based assays in modern biomedical research

Cell based assays are one of the most powerful tools for biomedical research, providing physiologically relevant environment for evaluating drug responses to cells, mechanistic studies, toxicity and can act as disease models. 2D cell culture models remain the standard choice to obtain valuable insights into the biological processes and drug effects. However, there is growing evidence that 2D models fail to represent typical tissue microenvironment and often result in ineffective in-vivo translation. To overcome these hurdles, 3D models have improved the success rate by offering better tissue microenvironment and higher biological relevance for drug development.

Why do cell-based screening matter

Cell based assays offer several advantages over biochemical assays, they allow researchers to:

• - Obtain physiologically relevant data in the living systems
• - Control cellular environment to better predict in vivo outcomes
• - Enable high throughput screening of thousands of compounds
• - Identify off-target effects and determine cytotoxicity in cells
• - Support mechanistic studies and providing insights into signalling pathways and gene expression.

Types of cell screening platforms

• • 2D cell culture model

This is the traditional cell-based model used for drug screening. They are suitable for high throughput screening (HTS) at reduced costs, most commonly used models include immortalised cell lines, primary cells and induced pluripotent stem cell (iPSC) derived cell types. 2D cultures are widely used for studying cell viability, basic phenotypic screening and mechanisms involved.

• • 3D cell culture model

3D organoids, spheroids and organ on chip models better present/ mimic extracellular components and tissue microenvironment compared to 2D monolayers (Fatehullah et al., 2016). These models have become increasingly popular due to their potential of increasing translatability, particularly in the therapeutic areas such as oncology, metabolic and neuroscience research.

• • Reporter gene and signalling assays

These assays utilise a genetically encoded fluorescent/ bioluminescence marker such as luciferase, GFP, etc to quantitively monitor biological response within the living cells (Zhang et al., 1999). The reporter assays are extremely useful in interrogating several signalling pathways. They offer high sensitivity and are routinely employed in HTS.

• • Cell based biosensors and chromatography

Using sensor technology` and separation techniques to evaluate cellular responses and drug interactions. Each platform has its own strengths, together forming a comprehensive package of drug discovery (Wei et al, 2021).

Applications in drug discovery

• Oncology: Cell based assays play a central role in assessing tumour cells proliferation, apoptosis and drug effects. Advanced models such as 3D spheroids better present intratumoral heterogeneity, extracellular matrix and thus making them a better model in comparison ton 2D monolayers.
• Immunology: Cell based platforms provide insights into the cytokine release, immune cell profiling and have become essential tools for immunotherapy. This enables filtering the compounds based on immune profiling before advancing to preclinical studies.
• Neuroscience: Neuronal based assays (and associated cell populations) are well-validated models to screen neuroprotective, neurotoxic and neuro-modulatory agents. iPSCs have contributes substantially to the early screening of compounds involved in this disease area.
• Personalised medicine: Patient derived tumour cells, organoids and tumour on chip models have enabled researchers to evaluate therapeutic responses in real patient samples. By utilizing patient specific tumour architecture, these models support personalised drug selection strategies.

References:

• 1. Amelian A, Wasilewska K, Megias D, Winnicka K. Application of standard cell cultures and 3D in vitro tissue models as an effective tool in drug design and development. Pharmacol Rep. 2017 Oct;69(5):861-870. doi: 10.1016/j.pharep.2017.03.014. Epub 2017 Mar 23. PMID: 28623710.


• 2. Fatehullah A, Tan SH, Barker N. Organoids as an in vitro model of human development and disease. Nat Cell Biol. 2016 Mar;18(3):246-54. doi: 10.1038/ncb3312. PMID: 26911908.


• 3. Wei F, Wang S, Gou X. A review for cell-based screening methods in drug discovery. Biophys Rep. 2021 Dec 31;7(6):504-516. doi: 10.52601/bpr.2021.210042. PMID: 37288368; PMCID: PMC10210057.


• 4. Zhang, J.-H., Chung, T. D., & Oldenburg, K. R. (1999). A simple statistical parameter for use in evaluation and validation of high throughput screening assays. Journal of Biomolecular Screening, 4(2), 67–73.

At TheraIndx, we have validated and reproducible cell-based screening assays which can also be customised based on your needs. Our expertise ensures that every study is conducted to highest standard with biologically relevant data to drive your drug discovery program forward.