Successful generation of human iPS cell-derived mesenchymal cells capable of producing alveolar organoids

Breathing intakes oxygen and expels carbon dioxide, and this gas exchange takes place in the alveoli in the lungs. Alveoli contain type 1 alveolar epithelial cells (AT1), which are involved in the actual gas exchange, and type 2 alveolar epithelial cells (AT2), which produce surfactants to prevent a collapse of the alveolar space. The interaction between epithelial cells and mesenchymal cells is essential for alveolar development.

In a previous study, the research group generated alveolar organoids containing AT1 and AT2 cells by co-culturing with human fetal lung fibroblasts (HFLFs) and used them for disease modeling. This new study aimed to create iPS cell-derived mesenchymal cells (iMES) that can induce alveolar epithelial cells, without using HFLFs.

The research group successfully generated iMES that can induce alveolar organoids (iMES-AOs) comprising not only AT2 cells but also AT1 cells, pulmonary neuroendocrine cells, and ciliated cells. Furthermore, they demonstrated that iMES-AOs could be used in influenza virus and SARS-CoV-2 infection models.

In the future, iMES-AOs are expected to be used in research on lung development and regenerative medicine, and respiratory disease models.

The results of this study were published online in Cell Reports Methods on September 19, 2022.