From Epithelium to Therapy: Transitional Cells in Lung Fibrosis.

Area of Science:

• Pulmonary Medicine
• Cell Biology
• Regenerative Medicine

Background:

• Idiopathic pulmonary fibrosis and infections like SARS-CoV-2 cause lung fibrosis with limited treatment options.
• Lung stem and progenitor cells are increasingly recognized for their role in lung fibrosis.
• The lung epithelium comprises diverse cell types, including stem and progenitor populations crucial for repair.

Purpose of the Study:

• To review lung epithelial cell functions and differentiation pathways.
• To focus on KRT5+ and KRT8+ transitional cells originating from alveolar type II cells.
• To discuss the role of these transitional cells in lung fibrosis and potential therapeutic strategies.

Main Methods:

• Review of existing literature on lung epithelial cells, stem cells, and fibrosis.
• Analysis of transitional cell populations (KRT5+, KRT8+) and their differentiation.
• Examination of cell and organoid therapy approaches for lung fibrosis.

Main Results:

• Two KRT5+ or KRT8+ transitional cell subpopulations, derived from alveolar type II cells, are key in lung regeneration and repair.
• These transitional cells aggregate near fibrotic foci in both animal models and human fibrotic lung disease, suggesting a role in pathogenesis.
• Recent advances include cell and organoid therapies aimed at replacing aberrant transitional cells.

Conclusions:

• Transitional cells play a critical role in lung repair and may contribute to fibrosis.
• Cell and organoid therapy, particularly using 3D organoids, shows promise for treating lung fibrosis.
• Strategies to improve cell engraftment and reduce immune clearance are vital for successful transplantation.