A “breathing” lung organoid enables measurement of lung stiffness

Tokyo, Japan — Researchers at the Institute of Industrial Science, The University of Tokyo have developed a system that allows human lung organoids to expand in a breathing-like manner by applying pressure from inside the tissue. The platform enables quantitative measurement of lung compliance—a mechanical indicator of how easily the lung expands—and may provide a new way to study diseases such as pulmonary fibrosis.

Reproducing breathing mechanics in organoid lungs

The lungs repeatedly expand and contract with each breath, and this mechanical flexibility is essential for normal gas exchange. However, most experimental lung models developed to date cannot reproduce these dynamic mechanical behaviors. Conventional organoid cultures replicate aspects of three-dimensional tissue structure but remain static systems without controlled mechanical stimulation.

To address this limitation, the research team developed Pulmonary Aciniform Organoids (PAcinOs) derived from human induced pluripotent stem cells. These organoids mimic the structure of the pulmonary acinus, the peripheral region of the lung where gas exchange occurs.

A device enabling access to the organoid interior

The researchers also designed a custom culture device called the Dynamic Exposure and Infusion Response Observer (DENIRO). This device allows researchers to access the internal lumen of organoids and apply controlled pressure.

By combining the PAcinO with the DENIRO platform and inserting a fine glass capillary into the organoid, its structure can be monitored using optical coherence tomography. This setup allows researchers to gradually increase the pressure inside the organoid and record the resulting three-dimensional volume changes.

Quantifying lung compliance in a human organoid model

Using this system, the researchers quantified lung compliance in lung organoids by measuring the relationship between pressure and volume changes.

When organoids were treated with bleomycin, a compound widely used to induce pulmonary fibrosis in experimental models, the organoids showed reduced expansion in response to pressure, indicating decreased compliance. Treatment with the antifibrotic drug nintedanib partially restored this response.

These findings demonstrate that mechanical changes associated with lung disease can be evaluated in a human induced pluripotent stem cell-derived three-dimensional organoid system.

Toward disease modeling and drug evaluation

By enabling simultaneous observation of organoid structure and mechanical function, the platform provides a new experimental approach for studying lung diseases characterized by tissue stiffening.

The researchers suggest that the system may support studies of pulmonary fibrosis and other respiratory diseases, and aid the evaluation of potential therapeutic drugs in human organoid models.

Journal: Biomaterials
Article Title: Dynamic in vitro platform for mechanical profiling of human pulmonary aciniform organoids via intraluminal access
DOI: 10.1016/j.biomaterials.2026.124094

About Institute of Industrial Science, The University of Tokyo

The Institute of Industrial Science, The University of Tokyo (UTokyo-IIS) is one of the largest university-attached research institutes in Japan. UTokyo-IIS is comprised of over 120 research laboratories—each headed by a faculty member—and has over 1,200 members (approximately 400 staff and 800 students) actively engaged in education and research. Its activities cover almost all areas of engineering. Since its foundation in 1949, UTokyo-IIS has worked to bridge the huge gaps that exist between academic disciplines and real-world applications.