Toward reconstruction of human lung tissue using iPS cells

Abstract

In recent years, long-term culture methods have been established for type II alveolar epithelial cells by organoid culture techniques. However, their cloning and long-term culture are still challenging. And there have been limited number of donors and chances of obtaining specimens, especially from patients with rare diseases or severe respiratory failure. Therefore, it has been difficult to study disease mechanisms and drug responses using human lung cells. The increasing availability of human pluripotent stem cells such as ES cells and iPS cells has made it possible to generate human lung cells, which are expected to compensate the difficulties of primary cells as well as animal experiments. Standardized cell lines are available for human ES cells. And human iPS cells can be generated from the donors if their peripheral blood are available for a research use. These days, we are able to choose methods of differentiation and post-differentiation culture, depending on the purposes. In this background, we have been working on disease models and seeking for implementing those methods for future regenerative medicine. One of our examples is disease modeling of pulmonary fibrosis that can recapitulate epithelial-mesenchymal interactions using alveolar organoids in co-culture of alveolar epithelium and fibroblasts. In addition, we have recently developed an “on-gel” culture method in which alveolar epithelial spheroids were formed on an extracellular matrix substrate, allowing improvement of the throughput of screening. Further, we have developed a micropatterned culture of apical-out alveolar and airway organoids in numerous aligned spots on the manufactured plates. I will talk about the latest topics in our laboratory.