June 24, 2025
Nagoya University, Tokai National Higher Education and Research System
Keio University
[Highlights of this research]
World's first successful generation of type II alveolar epithelial-like cells (iPUL cells) in approximately 7 days via direct reprogramming with four transcription factors (Nkx2-1, Foxa1, Foxa2, and Gata6).
iPUL cells exhibited lamellar body-like structures, and their gene expression profiles showed high homology with normal alveolar type 2 (AT2) cells.
When iPUL cells were administered to a mouse model of interstitial pneumonia (pulmonary fibrosis), engraftment in the alveolar region and partial differentiation into alveolar type 1 (AT1)-like cells were confirmed after 42 days.
This novel technology for generating pulmonary epithelial cells without the use of stem cells is expected to have applications in regenerative medicine.
In a joint research project with the University of Tokyo and others, a research group including Professor Makoto Ishii of the Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, and Professor Koichi Fukunaga, Assistant Professor Takanori Asakura, and Collaborative Researcher Atsuho Morita from the Division of Pulmonary Medicine, Department of Internal Medicine, Keio University School of Medicine, has achieved a world-first success: generating lung cells (type II alveolar epithelial-like cells) from mouse fibroblasts in the short period of approximately 7 days.
This study focused on "direct reprogramming technology," which alters cell fate without going through a stem cell stage, and used four transcription factors (Nkx2-1, Foxa1, Foxa2, and Gata6) to induce mouse cells into pulmonary epithelial-like cells. The induced cells, named "iPUL cells (inducedPULmonary epithelial-like cells)," showed lamellar body-like structures under an electron microscope and demonstrated high similarity to normal alveolar type 2 (AT2) cells in comprehensive gene analysis. Furthermore, when iPUL cells were intratracheally administered to a mouse model of pulmonary fibrosis, engraftment in the alveolar region was confirmed, and some cells were observed to differentiate into alveolar type 1 (AT1)-like cells.
This research is a breakthrough that opens a new path for regenerative medicine for the lungs, which have been considered difficult to restore once damaged. It is expected to lead to the future development of new curative treatments for intractable lung diseases such as interstitial pneumonia, COPD, and severe pneumonia.
The results of this research were published in the international scientific journal "npj Regenerative Medicine" from the Springer Nature group on June 23, 2025 (18:00 JST).
Please see below for the full press release.