In vitro lung models are experimental systems that aim to replicate lung structure and function outside of a living organism. By recreating parts of the lung in a controlled laboratory environment, these models allow researchers to study lung biology and test the effects of drugs, toxins, and other agents on lung tissue without using live animals. A wide range of in vitro models have been developed that range from simple monolayer cell cultures to more complex 3D organoids and microfluidic systems. Each model type offers advantages for particular research applications.
2D vs. 3D Cell Culture Models
Some of the simplest lung models involve growing lung cells in two dimensions on flat surfaces, such as on the bottom of cell culture plates. Known as 2D cultures, these systems are useful for initial drug screenings and studies of basic lung cell biology. However, 2D cultures lack the complex 3D architecture and cell-cell interactions found in real lung tissue. More advanced 3D lung models have been created to better mimic the native lung environment. These contain lung cells grown together in 3D gels or scaffolds to self-assemble into organoids that resemble the structures of lung airways, blood vessels, or alveoli. Compared to 2D cultures, 3D models typically exhibit improved physiological relevance for studies of lung development, disease, and treatment responses.
Microfluidic Models with Perfused Airways
To generate more lung-like living systems, researchers have incorporated fluid flow features into 3D In Vitro Lung Models. Microfluidic organ-on-a-chip devices allow for perfusion of cell cultures with fluid flowing through embedded microchannels. This flow mimics the movement of air through bronchioles or blood through capillaries in the lungs. Some advanced microfluidic lung chips even contain multiple cell types integrated across air-blood barriers. With dynamic fluid flow and tissue-tissue interfaces, these models can better replicate mechanical forces and whole organ functionality versus static cultures. Microfluidic lungs show promise for personalized medicine approaches and predictive preclinical safety/efficacy testing of inhaled drugs and toxins.
Applications in Drug Development and Disease Modeling
In vitro lung models are proving invaluable in biomedical research areas like drug development and disease modeling. In the pharmaceutical industry, 3D lung models and organ-on-chips are being used to complement or reduce animal testing during drug candidate screening and optimization. Models can assess drug absorption, metabolism/distribution within lung tissues, and toxicity risks earlier in development pipelines. Regarding disease modeling, in vitro systems containing lung cells from patients offer a way to recreate aspects of respiratory illnesses such as asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and COVID-19 outside of living patients. Researchers can use these disease-in-a-dish models to better understand disease mechanisms and identify new therapeutic strategies. Overall, global advancement of in vitro lung technologies is translation real lung physiology into the laboratory and yielding insights beneficial to human health.
Designing Models to Mimic Individual Lung Variability
While existing in vitro lung models have provided insights, they still have limitations versus real human lungs, which naturally exhibit significant inter-individual variability in structure and function. No single model can currently capture the full range of lung diversity found across different patients and demographics. However, emerging approaches may help design tissue models with personalized traits. For example, lung cells reprogrammed through induced pluripotency offer a way to culture 3D tissues from specific patients. Combined with cell isolation techniques, biomaterials, and organ-chip platforms, researchers are working on methods that will enable tailored modeling of individual lung phenotypes linked to clinical data. Such next-generation personalized lung models hold promise for advancing precision medicine approaches to diagnose, prognosticate, and treat a variety of lung conditions in a disease subtype-specific manner.
Global Collaboration Advancing In Vitro Lung Technologies
Given the pressing medical need for improved lung therapies and diagnostics, in vitro lung modeling has increasingly become a globally collaborative effort. Major initiatives supported by funding agencies, industries, and non-profits aim to standardize models, share protocols and best practices internationally, and accelerate translation of new technologies into applications. Some examples include the Lung Map Consortium sponsored by the US National Institutes of Health and the International Bridge consortium initially funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). These large consortia bring together academic labs, biotech startups, disease foundations, regulators and other stakeholders worldwide. They promote open data sharing, hold workshops on cutting-edge techniques, provide resources like 3D printable lung organs, and validate models for regulatory assessment across countries. Through such collaborations, in vitro models of the respiratory system are continually being enhanced to benefit global human health.
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