Regeneration of functional alveoli by adult human SOX9 airway basal cell transplantation.
10.1007/s13238-018-0506-y
- Author:
Qiwang MA
1
;
Yu MA
1
;
Xiaotian DAI
2
;
Tao REN
3
;
Yingjie FU
4
;
Wenbin LIU
1
;
Yufei HAN
1
;
Yingchuan WU
1
;
Yu CHENG
4
;
Ting ZHANG
5
;
Wei ZUO
6
Author Information
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. Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, China. zuow@tongji.edu.cn.
- Publication Type:Journal Article
- Keywords:
alveoli;
bronchiectasis;
lung;
regeneration;
stem cell;
transplantation
- MeSH:
Bronchiectasis;
genetics;
metabolism;
Humans;
Pulmonary Alveoli;
cytology;
metabolism;
SOX9 Transcription Factor;
genetics;
metabolism;
Stem Cell Transplantation;
methods;
Stem Cells;
cytology;
metabolism
- From:
Protein & Cell
2018;9(3):267-282
- CountryChina
- Language:English
-
Abstract:
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. Altogether 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.
