Establishment of safety evaluation system for tissue regeneration therapy by alveolar organoid transplantation

There are many refractory lung diseases such as lung cancer, chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Because the lung can not regenerate itself, lung regeneration therapy has been highly demanded. Alveolar epithelial type 2 (AT2) cells, which are the tissue stem cells in the lung, are considered to play a central role in the pathogenesis of these refractory diseases and are expected to be applied to regenerative medicine. However, research on AT2 cells has been delayed since an appropriate culture method of AT2 cells was not established so far. The principal investigator and his collegues developed the methods of robust and efficient generation of airway and alveolar epithelial cells from human induced pluripotent stem cells (hiPSCs). In order to evaluate the future risk of using hiPSCs for lung regeneration therapy, we make clear the heterogeneity of respiratory epithelial cells differentiated from hiPSCs and its significance, thereby clarifying the mechanisms that control the stem cell homeostasis in the lung from the viewpoint of bioinformatics. We aim to construct a safety assessment system at a single cell level for cell transplantation therapy.