Lung disease is one of the leading causes of death and morbidity all across the globe, affecting both young and old, and is particularly dangerous in children. Air pollution is one of the major contributors to lung disease. For instance, Delhi’s severe air pollution has put its kids at high risk because breathing toxic air leads to diseases like chronic obstructive pulmonary disease (COPD), lung cancer, and acute respiratory infections.
“Specific findings from lung tests show that 43.5% of the Delhi school children suffered from ‘poor or restrictive lungs,’ as compared to 22% of the kids in the rural schools.12 Alveolar macrophages (AM), lung cells that clean off microorganisms and dust particles, were 2-3 times more frequent in Delhi school children than in rural children.” – The Yale Global Health Review
Researchers must discover new therapies to combat lung diseases, given their severe repercussions. Up until now, scientists have been using traditional models like human cells grown in the lab in a dish (also called 2D cell culture) and animals like mice to study diseases. Although these models contributed to the development of modern medicine in the last four to five decades, they have their limitations. They often produce inaccurate results because they don’t completely represent the complex physiology of human tissues inside the body. Thus, researchers across the globe are working towards developing new efficient models to accurately predict drug action in a particular disease.
One such exciting model is the 3D Cell Culture which enables researchers to recapitulate the complexity of the human body in the lab. To understand more about this model, I recently talked to Dr. Tejal Pant, a freshly minted scientist from the Nanomedicine Research Group, who has worked on developing alternative models to study lung cancer as part of her Ph.D. research. “The remarkable advances in the field of 3D cell culture platforms have enabled their application for establishing disease models. They provide more relevant outcomes than traditional 2D cultures owing to their ability to more closely recapitulate the in vivo environment,” she said.
Dr.Pant’s research focused on establishing a 3D culture model of lung cancer cells to evaluate nanotechnology-based drugs. She developed lung cancer spheroids which are masses of aggregated lung cancer cells. The drugs were treated on both 2D cultures as well as 3D spheroids. The research demonstrated that 2D cultures were sensitive and readily died after treatment but 3D cultures were more resistant. This shows that 3D cultures like spheroids are a suitable model to evaluate the efficacy and toxicity of new drugs. You can access her research here.
“This [tool] could save millions of dollars that are spent for unsuccessful drug candidates [by the pharmaceutical companies] reducing the overall cost of research and development during pre-clinical and clinical trials.” – Dr. Tejal Pant.
Now, let us understand how these models are relevant to COVID-19. 3D culture structures like spheroids and organoids are a great tool to understand the disease mechanisms, evaluate drug effects, and could help reveal many things that other models cannot. Over the past two years, researchers have employed 3D cultures for COVID-19 research which has contributed a lot to the existing knowledge about the virus and infection, thus helping the global community. For instance, using 3D cell cultures researchers observed robust immune responses that led to cytokine storm in COVID-19 infection and how drugs like imatinib could decrease infection (Han et al.). In such a way, 3D cultures enable scientists to understand disease mechanisms as well as allow them to test and discover the right drugs for the infection.
Organoids that are 3D cultures resembling an organ can be a great tool for COVID-19 research because researchers can use them to observe how the virus infects other organs than the lungs such as the brain and kidney.
The efficiency and accuracy of the tools and techniques we employ will play a huge factor in determining the future of medicine. New-age tools like 3D cultures are a boon for researchers and scientists which offer a robust platform to understand diseases and devise new drugs and treat many life-threatening diseases.
Written by – Parth Choudhari, Science Communicator, Nanomedicine Research Group.