3D Cell Culture Models Are Driving the Fight Against Infectious Diseases Like Coronavirus | Corning

The coronavirus pandemic is turning the science of viruses into front-page news, but the bulk of the reporting tends to focus on statistical projections for viral infection. What gets less attention is the laboratory science that drives the quest to understand the biology of viruses and to use that understanding to develop new treatments and vaccines.

With 3D cell culture and other novel technologies at their disposal, researchers can advance viral and cellular science faster but also more predictably. 3D modeling is more predictive of those biological systems, making in vitro results more easily translated to human patients.

3D cell culture models are one of the indispensable technologies that are leading the fight against infectious diseases.

A Vital Tool in Need of Improvement

Studying any virus — whether the mechanisms of its infectiousness or the symptoms of its cellular effects — begins with identifying its associated cells and tissues. Once scientists determine the most important biological environments in which the virus acts, research can begin, provided that appropriate models are available. They need to isolate the virus, along with any variants, and watch how it performs as it does in nature, but human experiments are out of the question at early stages.

As a result, cell cultures of various kinds have always been used at almost every stage of disease research, including disease modeling, drug target identification and validation, potency profiling and toxicity assessment. They allow drug development in human-like models without the need to endanger a real human participant.

However, as vital a tool as it has been, traditional 2D cell culture models have always had a number of limitations.

Historically, researchers have leaned on 2D culture methods, but the obvious differences between plated cells and living biological tissues make research labor-intensive and prone to false starts. Right now, more than half of all drug trials fail in the second or third phase of clinical trials, according to a study published in Frontiers in Pharmacology. The potential new drugs move to more advanced stages of clinical trials due to promising early results, but then later drop out of the pipeline due to adverse effects that were not adequately predicted with the in vitro cell models used in the early phases of research.

This wastes precious, finite resources and funding. With a more realistic model available for early drug development and identification of false leads, delivery of new medicines could happen more rapidly and at a lower cost.

A More Efficient, Realistic Model

2D culturing methods are not fully representative of real tissues, so they provide a partial, yet incomplete look at real tissue function. 3D cell cultures, on the other hand, are an attempt to actually grow those tissues directly, with more of the complexity and experimental accuracy that implies.

A 3D culture better represents the physical and biochemical environment that viruses encounter in vivo. This has led to a wide array of new insights into the infectious action of pathogens, ranging from toxoplasma gondii to mycobacterium tuberculosis.

A recent study in Nature looked at the utility of 3D cell culture models mimicking the human bronchial and small airway cells in studying infectious respiratory disease. Their study found that 3D culturing methods efficiently produced biologically relevant results (host-pathogen interactions in respiratory tissues) that would have been difficult and time-consuming to produce using only existing 2D models.

Hubrecht Organoid Technology (HUB) in the Netherlands is currently using organoid models to study infectious diseases, including the creation of human lung organoids to study the effects of respiratory syncytial virus (RSV) on this system.

In general, as one recent study published by the American Society for Microbiology put it, 3D cell culture models "provide a more physiologically relevant and predictive framework for investigating infectious disease mechanisms and antimicrobial therapies." That means faster identification of compounds that could counteract or interfere with disease mechanisms and, through that, faster development of cures for infectious disease.

Working with cell cultures in three dimensions requires specialized tools, which are more readily available than ever. These tools include Corning® Matrigel® matrix, which mimics the extracellular matrix to provide both physical scaffolding and relevant growth factors, and newer technologies such as ultra-low attachment surfaces, which enable scaffold-free culture development.

High-throughput and high capacity technologies for generation and assaying of 3D spheroid cultures are examples of how the accuracy of studies on 3D cellular structures could soon meet the high throughput of legacy 2D technologies.

Overcoming the Next Decade's Challenges

The scientific world never sits on a breakthrough for long. Already, researchers are using 3D cell culturing technology to network organoids into organ-on-a-chip configurations. These configurations enable comprehensive, organ-specific models while remaining a relatively quick and readily available lab tool. In the future, bioprinters could design and fabricate new and better 3D cell cultures with ease.

In the fight against infectious diseases, like coronavirus and potentially similar viruses that resist legacy antiviral medications, doctors and researchers will need better tools than ever before. Scientists need to fast-track every step in the drug development process without compromising the accuracy of their results. With modern 3D cell culture models and other specialized technologies in hand, they may now have the tools they need to do it.