Amniotic fluid mesenchymal stem cells ameliorate lung alveolar epithelium regeneration and reverse lung fibrosis of chronic obstructive pulmonary disease

Abstract

Pulmonary emphysema progression is attributed not only to alveolar structure loss and pulmonary regeneration impairment but also to excessive inflammatory response, proteolytic and anti‐proteolytic activity imbalance, lung epithelial cell apoptosis and abnormal lung remodeling. To ameliorate lung damage with higher efficiency through lung tissue engineering and cell therapy, predifferentiating graft cells into more restricted cell types before transplantation could enhance their ability to anatomically and functionally integrate into damaged lung. An optimal lung epithelial progenitor‐like cells (LEPLCs) predifferentiation condition has been established in eGFP‐expressing amniotic fluid mesenchymal stem cells (AFMSCs). Transplantation of LEPLCs significantly improved regeneration of lung tissue as they integrated into the lung alveolar structure, relieved airway inflammation, alleviated amount of DNA damage in alveolar cells, increased expression of growth factors such as vascular endothelial growth factor, and reduced expression of matrix metalloproteinases and lung remodeling factors when compared with the elastase‐induced pulmonary emphysema mice injected with AFMSCs. In conclusion, transplantation of predifferentiated AFMSCs through intratracheal injection showed better alveolar regeneration and reverse lung fibrosis in PPE‐induced pulmonary emphysema mice.Support or Funding InformationThis research was supported by grant MOE‐108‐S‐0023‐A from the Ministry of Education of Taiwan.