Intrapulmonary distal airway stem cell transplantation repairs lung injury in chronic obstructive pulmonary disease

Objectives Chronic 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 Methods Mouse 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. Results We 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. Conclusions The 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. Mouse and human DASCs could be indefinitely expanded and were able to further differentiated into mature alveolar structures during in vitro cultures. Single‐cell analysis indicated that the engrafted cells expressed typical cellular markers of type I alveolar cells as well as the specific secreted proteins. Transplantation of human DASCs derived from chronic obstructive pulmonary disease (COPD) patients into the lungs of NOD‐SCID mice with COPD repaired the tissue damage and improved the pulmonary function.