A New Era of “Breathing” Human Lung Organoids — Technology for Reproducing Dynamic Lung Mechanics Published in Biomaterials —

HiLung Inc. is pleased to announce the development of pulmonary aciniform organoids (PAcinO), which mimic the pulmonary acinus, the peripheral functional structure of the human lung, through a collaborative research project with Professor Shoji Takeuchi, Professor at the Institute of Industrial Science, The University of Tokyo (also Professor at the Graduate School of Information Science and Technology, The University of Tokyo).

In this research, Yuki Yamamoto, CEO of HiLung Inc., served as a co-corresponding author. HiLung team members, including Shogo Nagata, Harry Choi, Toshio Suzuki, and Tetsuharu Nagamoto, also contributed to the technology development, helping establish a novel experimental platform capable of reproducing both the three-dimensional architecture of the human lung and its dynamic breathing mechanics.

The research group further developed DENIRO (Dynamic Exposure and Infusion Response Observer), a device that enables direct access to the interior of the organoid and allows pressure to be applied from the luminal side. By integrating PAcinO with DENIRO, the team established an experimental system called “PAcinOs in DENIRO.” Using optical coherence tomography (OCT) for non-invasive three-dimensional observation, the researchers successfully quantified pressure-induced changes in organoid volume as well as lung compliance.

In addition, by applying bleomycin, a compound known to induce fibrosis, the team reproduced fibrosis-like mechanical stiffening in PAcinO and evaluated the effects of currently available anti-fibrotic drugs. These results demonstrate that this technology is not limited to structural recapitulation alone, but also has strong potential as a disease modeling and drug evaluation platform.

Conventional two-dimensional culture systems have had clear limitations in reproducing the three-dimensional architecture of the lung and its mechanical responses during breathing. In addition, in commonly used organoid culture systems derived from human tissues, luminal structures are often absent or too small to allow direct access and precise manipulation.

In contrast, this study leveraged human iPSC-derived cellular engineering to create organoids with a size and structure that more closely resemble the grape-like architecture of the native lung. By enabling access to the organoid lumen, this platform makes it possible to evaluate dynamic mechanical responses while preserving the three-dimensional structure, representing a significant technical advance.

This achievement is expected to advance our understanding of the fine structure and biomechanics of the human lung, which are extremely difficult to observe directly in vivo. It may also contribute to the study of diseases characterized by lung stiffening and reduced compliance, including pulmonary fibrosis, as well as to the evaluation and development of new therapeutic candidates.

HiLung will continue to leverage its human iPSC-derived respiratory organoid technologies and collaborate with both academia and industry to accelerate respiratory disease research and drug discovery.

For further details, please see:
[Press Release] “Breathing” Lung Organoids!? — Reproducing Dynamic Breathing Mechanics with Human Lung Organoids —
The University of Tokyo, Institute of Industrial Science

Publication details
Journal: Biomaterials (online edition published on February 26, 2026)
Article title:
Dynamic in vitro platform for mechanical profiling of human pulmonary aciniform organoids via intraluminal access

https://www.sciencedirect.com/science/article/pii/S0142961226001183?via%3Dihub