Regeneration of functional alveoli by adult human SOX9 airway basal cell transplantation
Protein & Cell
;
(12): 267-282, 2018.
Article
Dans Anglais
| WPRIM
| ID: wpr-757999
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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Alvéoles pulmonaires
/
Cellules souches
/
Dilatation des bronches
/
Biologie cellulaire
/
Transplantation de cellules souches
/
Facteur de transcription SOX-9
/
Génétique
/
Métabolisme
/
Méthodes
Type d'étude:
Étude pronostique
Limites du sujet:
Humains
langue:
Anglais
Texte intégral:
Protein & Cell
Année:
2018
Type:
Article
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