Fegeneration of functional alveoli by adult human SOX9^＋ airway basal cell transplantation  

作　　者：Qiwang Ma Yu Ma Xiaotian Dai Tao Ren Yingjie Fu Wenbin Liu Yufei Han Yingchuan Wu Yu Cheng Ting Zhang Wei Zuo 

机构地区：[1]Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China [2]Southwest Hospital, Third Military Medical University of PLA, Chongqing 400038, China [3]Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China [4]The Institute for Biomedical Engineering and Nano Science, School of Medicine, Tongji University, Shanghai 200029, China [5]Kiangnan Stem Cell Institute, Zhejiang 311300, China [6]Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China

出　　处：《Protein & Cell》2018年第3期267-282,共16页蛋白质与细胞（英文版）

摘　　要：Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9^＋ basal cells （BCs） located at airway epithelium rugae can regenerate adult human lung. Human SOX9^＋ BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9^＋ BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient＇s lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9^＋ BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3-12 months after cell transplantation. Alto- gether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future.Irreversible destruction of bronchi and alveoli can lead to multiple incurable lung diseases. Identifying lung stem/progenitor cells with regenerative capacity and utilizing them to reconstruct functional tissue is one of the biggest hopes to reverse the damage and cure such diseases. Here we showed that a rare population of SOX9^＋ basal cells （BCs） located at airway epithelium rugae can regenerate adult human lung. Human SOX9^＋ BCs can be readily isolated by bronchoscopic brushing and indefinitely expanded in feeder-free condition. Expanded human SOX9^＋ BCs can give rise to alveolar and bronchiolar epithelium after being transplanted into injured mouse lung, with air-blood exchange system reconstructed and recipient＇s lung function improved. Manipulation of lung microenvironment with Pirfenidone to suppress TGF-β signaling could further boost the transplantation efficiency. Moreover, we conducted the first autologous SOX9^＋ BCs transplantation clinical trial in two bronchiectasis patients. Lung tissue repair and pulmonary function enhancement was observed in patients 3-12 months after cell transplantation. Alto- gether our current work indicated that functional adult human lung structure can be reconstituted by orthotopic transplantation of tissue-specific stem/progenitor cells, which could be translated into a mature regenerative therapeutic strategy in near future.

关 键 词：lung regeneration TRANSPLANTATION stem cell. bronchiectasis ALVEOLI 

分 类 号：S823[农业科学—畜牧学] Q344.2[农业科学—畜牧兽医]