Abstract
Chronic respiratory diseases are a major global health concern. Lung epithelial dysfunction is a common underlying feature of many such conditions; hence, reconstructing the diseased epithelium with functional epithelial cells is a promising therapeutic approach. There are various endogenous stem cell and progenitor populations in the lung epithelium that can be utilized for transplantation. Additionally, pluripotent stem cells (PSCs) have emerged as a valuable source for generating therapeutic cells due to their capacity for indefinite self-renewal and the availability of directed differentiation protocols to transform them into lung progenitors or mature lung epithelial cells. This review discusses the endogenous stem cell and progenitor populations of the lung epithelium, recent advances in developing directed differentiation protocols to generate these cells, and the application of both endogenous and PSC-derived lung epithelial cells for disease modeling in vitro and as cell therapies in vivo. It provides valuable insights into the current progress of regenerative medicine within the respiratory field and highlights areas that require further research.