Regeneration of functional alveoli by adult human SOX9+ airway basal cell transplantation
| Autor: | Yu‐fei Han, Wei Zuo, Yingchuan Wu, Wenbin Liu, Xiaotian Dai, Yingjie Fu, Ting Zhang, Yu Cheng, Qiwang Ma, Tao Ren, Yu Ma |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty bronchiectasis Population lcsh:Animal biochemistry Biochemistry Pulmonary function testing lung 03 medical and health sciences 0302 clinical medicine Drug Discovery medicine Humans Progenitor cell lcsh:QH573-671 education lcsh:QP501-801 education.field_of_study alveoli Lung business.industry lcsh:Cytology Regeneration (biology) Stem Cells SOX9 Transcription Factor Cell Biology respiratory system respiratory tract diseases Transplantation stem cell Pulmonary Alveoli 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis regeneration Respiratory epithelium Stem cell business Biotechnology Research Article transplantation Stem Cell Transplantation |
| Zdroj: | Protein & Cell Protein & Cell, Vol 9, Iss 3, Pp 267-282 (2018) |
| ISSN: | 1674-8018 1674-800X |
| Popis: | 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. Electronic supplementary material The online version of this article (10.1007/s13238-018-0506-y) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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