Distal Airway Stem Cells Seen to Block Fibrosis, Support Tissue Growth in PF Mouse Model

Distal airway stem cells (DASCs), which can differentiate into bronchioles and alveoli, were found to prevent fibrosis and support tissue regeneration in the lungs of mice.

These findings were reported in the study “Distal airway stem cells ameliorate bleomycin-induced pulmonary fibrosis in mice,” published in the journal Stem Cell Research & Therapy.

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung tissue scaring and changes in cellular integrity, which lead to a loss of normal lung architecture. But its underlying mechanisms are still poorly understood.

Increasing evidence suggests that some populations of stem cells can promote tissue regeneration, and reverse the damage to lung tissue and vessels caused by IPF. DASCs, in particular, have shown a regenerative capacity after lung injury.

This population of stem cells appears to be highly activated upon damage, migrating to damaged areas where they undergo differentiation to replace the missing cells.

Researchers in China explored whether DASCs could reverse the effects of pulmonary fibrosis (PF) in a mouse model of the disease.

The team chemically induced PF by exposing mice to bleomycin. Seven days later, they analyzed the animals’ lungs and found that DASCs, which could be detected by the presence of KRT5 and P63 proteins, were located close to the bronchioles and alveolar space (where gas exchange occurs in the lungs).

Although the DASCs seemed to be contributing to the repair process, their low numbers low were not enough to overcome the extensive damage caused by bleomycin. So the researchers transplanted DASCs collected from healthy mice into the PF mice.

These additional cells effectively populated diseased tissue in the lungs of the PF mice, while in healthy lungs they had no detectable impact, suggesting that DASCs have a “special incorporation ability” in damaged tissue.

Further analysis revealed that the mice with transplanted DASCs had fewer lung tissue lesions compared to untreated PF mice. DASCs were also seen to effectively prevent tissue remodeling and collagen accumulation.

Overall, PF mice with a transplant of DASCs showed healthier post-injury pulmonary function and extended survival compared to untreated PF mice.

Supported by these findings, the team believes that “DASCs could be an ideal candidate stem cell for the therapy of pulmonary fibrosis.”

These cells can have a “lung-protective effect” due to their ability to contribute to “lung regeneration and prevention of pulmonary fibrosis development,” the researchers concluded.