Domestic researchers have developed a new human lung model to replace animal testing. This is expected to overcome the limitations of existing animal models and contribute to increasing the precision of infectious disease research and respiratory drug development.
Research teams led by Mi-Ok Lee of the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Stem Cell Fusion Research Center and Jeong-Hyun Kim, a researcher at the Disease Control and Prevention Agency and professor at Ajou University College of Pharmacy, jointly developed a 'pulmonary alveolar assembloid (iAlvAssemb)' that can mimic the actual human lung environment, they announced on the 15th. The study results were published in the international journal 'Nature Communications' on Apr. 9.
Organolds are mini-organs created using stem cells in a three-dimensional structure, which allows for the reproduction of physiological environments similar to human organs by partially simulating the structure and function of actual organs. The importance of organoid technology is increasing as the U.S. Food and Drug Administration (FDA) announced on Apr. 10 a 'roadmap for reducing animal testing in preclinical safety assessments.'
In particular, the lungs are an organ that comes into direct contact with external air, being the first to be exposed to harmful substances such as viruses, bacteria, and fine dust. At this time, alveolar epithelial cells and resident macrophages cooperate as the first line of defense to regulate the initial immune response. Until now, research on these immune functions has primarily relied on animal models such as mice, but an organoid that accurately replicates the actual human lung, including immune cells, was necessary.
The research team created an 'induced pulmonary alveolar assembloid' that can reproduce the structure and immune response of actual human lungs by co-culturing alveolar epithelial-like cells induced from human stem cells with macrophage-like cells. They also successfully optimized the differentiation and functional characteristics of both cell types and established customized culture conditions for co-culturing to stably maintain cell-to-cell interactions.
The organoid can precisely replicate functions performed by actual alveolar macrophages, such as the removal of damaged epithelial cells, absorption of oxidized lipids, and responses to tuberculosis infection. The research team noted, "We are currently utilizing this in research on severe novel coronavirus infection (COVID-19) and high-risk avian influenza" and explained, "The National Preclinical Research Center (KPEC) is using it to evaluate the efficacy of respiratory virus therapeutic candidates developed in collaboration with academia and industry."
Mi-Ok Lee noted, "The absence of immune cells has been pointed out as a major functional limitation in organoid research. This study has developed a new three-dimensional research platform for lung damage and infectious disease research, and we expect that the rapid and accurate simulation of lung immune responses using the pulmonary alveolar assembloid will contribute to the development of lung regeneration drugs and rapid responses to new infectious diseases."
References
Nature Communications (2025), DOI: https://doi.org/10.1038/s41467-025-58450-w