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This review examines endogenous lung epithelial stem and progenitor populations and recent methods for directed differentiation. It evaluates how endogenous and pluripotent stem cell–derived lung epithelial cells support in vitro disease modeling and in vivo cell therapies. The synthesis highlights current regenerative medicine progress for lung epithelial repair and identifies priorities for further research.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/recent-advancements-in-the-generation-and-application-of-therapeutic-cell-populations-for-lung-epithelial-repair/407843/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/recent-advancements-in-the-generation-and-application-of-therapeutic-cell-populations-for-lung-epithelial-repair/407843.png","ImageObject",300,407,{"name":92,"@type":93},"Adam","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-28",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why focus on lung epithelial repair in chronic respiratory diseases?","Question",{"text":112,"@type":113},"Lung epithelial dysfunction is a shared underlying feature across many chronic respiratory conditions, and reconstructing the diseased epithelium with functional epithelial cells is a promising therapeutic direction.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What role do pluripotent stem cells (PSCs) play in generating therapeutic lung cells?",{"text":117,"@type":113},"PSCs are highlighted as a valuable source due to indefinite self-renewal and directed differentiation protocols that produce lung progenitors or mature lung epithelial cells.",{"name":119,"@type":110,"acceptedAnswer":120},"How are lung epithelial cells used beyond transplantation?",{"text":121,"@type":113},"The review describes using endogenous and PSC-derived lung epithelial cells for disease modeling in vitro and for evaluating therapeutic functionality and efficacy in vivo.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},407843,1790714073,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":31,"preview_page_count":4},1374404737137,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Wiley  \nJournal of Tissue Engineering and Regenerative Medicine Volume 2025, Article ID 8367426, 20 pages [https://doi.org/10.1155/term/8367426](https://doi.org/10.1155/term/8367426)  \nReview Article  \nRecent Advancements in the Generation and Application of Therapeutic Cell Populations for Lung Epithelial Repair  \nMuyang Zhou , 1,2 Dana Brinson , 1,3 Cindy Lei , 1,4 and Golnaz Karoubi 1,2,5  \n1 Latner Toracic Research Laboratories, University Health Network, Toronto, Ontario, Canada  \n2 Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto,  \nOntario, Canada  \n3 Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada  \n4 Department of Molecular Genetics, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada  \n5 Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, Ontario, Canada  \nCorrespondence should be addressed to Golnaz Karoubi; [golnaz.karoubi@utoronto.ca](golnaz.karoubi@utoronto.ca)  \nReceived 6 May 2025; Revised 19 November 2025; Accepted 5 December 2025  \nAcademic Editor: Catherine K. Kuo  \nCopyright © 2025 Muyang Zhou et al. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons Ltd. Tis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \nChronic 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. Tere 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 indefnite self-renewal and the availability of directed diferentiation protocols to transform them into lung progenitors or mature lung epithelial cells. Tis review discusses the endogenous stem cell and progenitor populations ofthe lung epithelium, recent advances in developing directed diferentiation 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 feld and highlights areas that require further research.  \nKeywords: cell therapy; directed diferentiation; disease modeling; lung epithelial regeneration; pluripotent stem cells; respiratory diseases  \n1. Introduction  \nChronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), cystic fbrosis, and pneumoconiosis, are among the most prevalent noncommunicable diseases worldwide [1] . Many of these conditions have a poor prognosis and will inevitably progress to an end stage, leading to lung failure. Existing therapies are mostly targeted toward alleviating symptoms, with none ofering a curative solution. It is widely acknowledged that lung epithelial dysfunction is an integral and shared component across many chronic respiratory diseases. Terefore, cell therapy aiming at reconstructing the  \ndiseased lung epithelium with normal, functional cells has emerged as a promising approach in recent years.  \nVarious cell populations can facilitate the repair and regeneration of lung tissue and thus have been considered for cell therapy. Multipotent bone marrow–derived cells (BMCs) attracted signifcant interest at the start of the century, largely fueled by several studies that reported the presence of intravenously infused BMCs in the lungs of recipient animals [2, 3] . However, their true engraftment and functional efcacy have b","cbCaijTe0wH0B7WF","https://ap.wps.com/l/cbCaijTe0wH0B7WF","pdf",1634625,"English","# Introduction\n# Endogenous Stem Cells and Progenitor Populations in the Lung Epithelium","[{\"question\":\"Why focus on lung epithelial repair in chronic respiratory diseases?\",\"answer\":\"Lung epithelial dysfunction is a shared underlying feature across many chronic respiratory conditions, and reconstructing the diseased epithelium with functional epithelial cells is a promising therapeutic direction.\"},{\"question\":\"What role do pluripotent stem cells (PSCs) play in generating therapeutic lung cells?\",\"answer\":\"PSCs are highlighted as a valuable source due to indefinite self-renewal and directed differentiation protocols that produce lung progenitors or mature lung epithelial cells.\"},{\"question\":\"How are lung epithelial cells used beyond transplantation?\",\"answer\":\"The review describes using endogenous and PSC-derived lung epithelial cells for disease modeling in vitro and for evaluating therapeutic functionality and efficacy in vivo.\"}]","Recent Advancements in the Generation and Application of Therapeutic Cell Populations for Lung Epithelial Repair | PDF",1790576428]