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From Epithelium to Therapy: Transitional Cells in Lung Fibrosis
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From Epithelium to Therapy: Transitional Cells in Lung Fibrosis
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Journal Article
From Epithelium to Therapy: Transitional Cells in Lung Fibrosis
2025
Overview
Abstract
Patients with idiopathic pulmonary fibrosis and lung fibrosis secondary to infections such as influenza A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have limited treatment options outside of supportive therapy and lung transplantation. Multiple lung stem cell populations have been implicated in the pathogenesis of lung fibrosis, and more progenitor cell populations continue to be discovered and characterized. In this review, we summarize the functions and differentiation pathways of various cells that constitute the lung epithelium. We then focus on two subpopulations of KRT5+ or KRT8+ transitional cells that both originate from alveolar type II cells but experience different cell fates and play important roles in lung regeneration and repair. We address these transitional cells’ potential role in fibrosis and bronchiolization of the alveoli, as they are correlated to aggregate near fibrotic foci in both in vivo models and in human fibrotic lung disease. We conclude by discussing recent advances in cell and organoid therapy to replace aberrant transitional cells and treat lung fibrosis. Namely, we focus on strategies to minimize immune clearance of transplanted cells and to optimize engraftment by transplanting cells precultured as three-dimensional organoids.
Publisher
Oxford University Press,American Thoracic Society
Subject
Alveolar Epithelial Cells - metabolism
/ Alveolar Epithelial Cells - pathology
/ Alveoli
/ Animals
/ Cells
/ Fibrosis
/ Humans
/ Idiopathic Pulmonary Fibrosis - pathology
/ Idiopathic Pulmonary Fibrosis - therapy
/ Pulmonary Fibrosis - pathology
/ Pulmonary Fibrosis - therapy
