3D Cell Culture Tissue Models for Drug Screening | Corning

Drug screening is an expensive process that requires many different steps to achieve success. Full commercialization often fails for many drug candidates, with 90% failing in clinical development and 80% stalling at pre-clinical development, failing to reach Phase I trials. However, emerging tissue model technology shows promise as a solution.

3D cell culture in the form of spheroids, organoids, and organ-on-a-chip (OoC) technology can offer physiologically relevant and human equivalent substitutes to animal and 2D in-vitro testing. With the ability to scale up and maintain consistency, tissue models may be the future for drug discovery and drug screening.

Why Use 3D Cell Culture for Drug Discovery and Screening?

Creating relevant human physiological tissue models through 3D cell culture is the future for cell-based assays. For example, cytotoxicity studies are faster and provide more comprehensive data since the 3D tissue models reflect what is going on at the organ level in terms of disease and response to drugs. 3D cell culture tissue models can also drive research in personalized medicine, helping to identify individuals' responses to drugs.

Instead of in-vitro cultures composed entirely of a single cell type, stem cell culture, and 3D bioprinting create tissue models that mimic cellular orientation and organ anatomy. Using support matrices such as Corning® Matrigel® matrix can help to scaffold and orient the different cell types in a culture.

Frontiers in Medical Technology notes that being able to accurately recreate tissues in 3D helps with biological relevance to living tissue. Combining these in hybrid forms with microfluidics as an OoC lets researchers examine responses to drugs in individual organs, or even as connected multiple organ models.

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Tissue Models for Drug Screening

Nervous System: Nerve-on-a-chip and mini brain models for peripheral and central nervous system research can enable drug screening in neurodegenerative disease and cancer models. Not only do they encompass myelination factors, but these in-vitro approaches also tackle tricky blood-brain barrier issues not represented by 2D culture. For example, growing 3D glioblastoma spheroids in microplate culture with permeability inserts such as the Transwell® system lets researchers examine the impact of chemotherapeutics and their cytotoxicity. Studies also include research into Parkinson's Disease, Multiple Sclerosis, and dementia.

Respiratory System: Lung- and airway-OoC models give researchers physiologically relevant approaches to drug screening for conditions such as asthma and chronic obstructive pulmonary disease. Tissue culture with Transwell and other Falcon® permeable supports allows air interphase analysis. Tissue models created from patient cells can assist in personalized medicine drug screening. For instance, cystic fibrosis involves many different genetic mutations, so screening an individual could help to predict drug response.

Hepatic Models: Since the liver is a complex multicellular organ that's responsible for metabolizing drugs into active states as well as detoxifying them safely into waste products, hepatic drug screening often requires in-vivo animal studies. The results of these studies are not always relevant to human physiology. Creating physiologically relevant co-cultures of different human cell types as a liver tissue model can help with drug and toxicity screening.

Muscle Tissue: Myocardial and skeletal muscle co-cultures usually retain muscle fiber contractility and calcium channel responses, making them ideal tissue models for examining cardiac drugs and investigating degenerative diseases. They're also physiologically relevant in screening for cardiotoxicity.

Oncology: Drug discovery studies often rely on using hard-to-source cells, such as those obtained from a patient's cancer biopsy. Archives in Toxicology notes that tissue models are useful for screening chemotherapy drugs to identify the best therapeutic choice. Factors such as genetic mutations, cell surface receptors, and other cell-specific features all play a role in determining therapeutic responsiveness.

In summary, using 3D cell culture to create authentic and valid tissue models helps researchers explore solutions to complex clinical problems, including cancer and personalized medicine. The ability to examine whole tissue responses in vitro is a powerful tool for clinical success.

Ready to get started in 3D cell culture? Learn more about tools available to support 3D models.

 
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