Evidence of increased pluripotent cells in adult human lung tissue derived from fibrotic lungs compared to non-fibrotic control lungs

Abstract

Introduction: Tissue-specific multipotent stem cells have been identified in the human lung. However, their role in lung homeostasis or lung disease is not clear. Methods: Primary human lung cells were cultured from fibrotic adult lung parenchyma (n=14) and from non-fibrotic control lungs (n=17). The characterization of different cell types was performed by immunofluorescence stainings. Results: Undifferentiated primary cells grew from adult human lung parenchyma, showing neither a clear epithelial nor mesenchymal morphology/immunofluorescence typing (=intermediate cells). When cultured in the respective appropriate media, intermediate cells transformed into mesenchymal cells (positive for fibronectin and α–smooth muscle actin) or into alveolar epithelial type II cells (positive for E-cadherin and surfactant protein-A). Pluripotency of intermediate cells was proven by positive stainings for Oct3/4 and NANOG. Successful induction of adipogenic, osteogenic, myogenic, and chondrogenic differentiation was performed in intermediate cells. Finally, significantly more pluripotent cells were generated from fibrotic lung tissue (n=14) than from non-fibrotic controls lungs (n=17). Conclusions: Our data demonstrate that adult human lung contains pluripotent cells which are able to differentiate towards an epithelial as well as a mesenchymal cell type solely by changing their microenvironment. These pluripotent cells might have a pivotal function in lung homeostasis and tissue repair. The observed increased incidence of these cells in fibrotic lung tissue suggests a role in fibrogenesis.