New pulmonary fibrosis inhalation therapy shows promise in mouse model

Lung stem cell secretions – nanosized exosomes and secretomes – delivered via a nebulizer has been shown to help in the repair of lung injuries from pulmonary fibrosis in mice and rats in research led by a team from North Carolina State University (NC State; USA).

Pulmonary fibrosis is a fatal and incurable disease characterized by a thickening and scarring of healthy lung tissue, inflammation and replacement of lung cells with fibrotic tissue. The current treatment options for pulmonary fibrosis are severely limited and not very effective apart from highly invasive lung transplants. To rectify this, Ke Cheng of NC State led the research into developing spheroid-produced lung stem cells (LSCs) as a potential therapeutic.

“The mixture of cells in LSCs recreates the stem cells’ natural microenvironment – known as the stem cell niche – where cells secrete exosomes to communicate with each other just as they would inside your body,” Cheng explained. “LSCs secrete many beneficial proteins and growth factors known collectively as ‘secretome’ – exosomes and soluble proteins, which can reproduce the regenerative microenvironment of the cells themselves. In this work we took it one step further and tested the secretome and exosomes from our spheroid-produced stem cells against two models of pulmonary fibrosis.”

Cheng’s lab used mouse and rat models of chemically, silica- or particle-induced pulmonary fibrosis to test lung spheroid cell secretome (LSC-Sec) and lung spheroid cell exosomes (LSC-Exo) against commonly used mesenchymal stem cells (MSCs). The stem cell-derived therapeutics – proteins, small molecules and nanosized exosomes – were delivered via inhalation directly to the lungs by a nebulizer.

In the mouse model of chemically induced fibrosis, improvements were seen in all stem cell therapies compared to the control, with a 32.4% reduction in fibrosis with MSC-Sec treatment and nearly 50% reduction with LSC-Sec treatment.

In the silica-induced fibrosis mouse model LSC-Sec treatment led to a 26% reduction in fibrosis compared to 16.9% with MSC-Sec treatment.

“This work shows that lung spheroid cell secretome and exosomes are more effective than their mesenchymal stem cells counterparts in decreasing fibrotic tissue and inflammation in damaged lung tissue,” Cheng stated. “Hopefully we are taking our first steps toward an efficient, non-invasive and cost-effective way to repair damaged lungs.

“Given the therapy’s effectiveness in multiple models of lung fibrosis and inflammation, we are planning to expand the test into more pulmonary diseases, including chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and pulmonary hypertension (PH).”

“The finding that products released by lung stem cells can be just as efficacious, if not more so, than the stem cells themselves in treating pulmonary fibrosis can be a major finding that can have implications in many other diseases where stem cell therapy is being developed,” commented Kenneth Adler, Professor at NC State and a co-author of the paper.

SOURCE

• Dinh PC, Paudel D, Brochu H et al., Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis. Nat. Commun. 11, 1064. (2020).