Intrapulmonary distal airway stem cell transplantation repairs lung injury in chronic obstructive pulmonary disease |
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Authors: | Xiaofan Wang Yu Zhao Dandan Li Yun Feng Yusang Xie Yueqing Zhou Min Zhou Yujia Wang Jieming Qu Wei Zuo |
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Institution: | 1. East Hospital, School of Medicine, Tongji University, Shanghai China ; 2. Department of Respiratory and Critical Care Medicine, School of Medicine, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai China ; 3. Kiangnan Stem Cell Institute, Zhejiang China ; 4. Ningxia Medical University, Yinchuan China ; 5. The First Affiliated Hospital, Guangzhou Medical University, Guangzhou China |
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Abstract: | ObjectivesChronic obstructive pulmonary disease (COPD) is characterized by irreversible lung tissue damage including chronic bronchitis and emphysema, which could further develop into respiratory failure. Many studies have revealed a potential regenerative function of the distal airway stem/progenitor cells (DASCs) after lung injury.Materials and MethodsMouse and human DASCs were expanded, analysed, and engrafted into injured mouse lungs. Single‐cell analyses were performed to reveal the differentiation path of the engrafted cells. Finally, human DASCs were transplanted into COPD mice induced by porcine pancreatic elastase (PPE) and lipopolysaccharide (LPS) administration.ResultsWe showed that isolated mouse and human DASCs could be indefinitely expanded and were able to further differentiate into mature alveolar structures in vitro. Single‐cell analysis indicated that the engrafted cells expressed typical cellular markers of type I alveolar cells as well as the specific secreted proteins. Interestingly, transplantation of human DASCs derived from COPD patients into the lungs of NOD‐SCID mice with COPD injury repaired the tissue damage and improved the pulmonary function.ConclusionsThe findings demonstrated that functional lung structure could be reconstituted by intrapulmonary transplantation of DASCs, suggesting a potential therapeutic role of DASCs transplantation in treatment for chronic obstructive pulmonary disease. |
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Keywords: | cell transplantation chronic obstructive pulmonary disease distal airway stem/progenitor cells single‐ cell sequencing |
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