PULMONARY fibrosis, a life-threatening disease caused by the damaging and scarring of lung tissue, currently has limited treatment options and no effective therapies besides lung transplant. However, a novel study shows that lung spheroid cell secretome and exosome inhalation can aid repair lung pulmonary fibrosis injuries in mice and rats.
Prof Ke Cheng, Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, North Carolina, USA, and his team have developed spheroid-produced lung stem cells as a potential therapeutic for pulmonary fibrosis. Lung spheroid cells (LSC), composed of a mixture of cells, recreate the stem cell niche allowing the cells to secrete exosomes to communicate with one another as they would in vivo. According to Prof Cheng: “LSC 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.” This study further utilised the secretome and exosomes from the spheroid-produced stem cells against two models of pulmonary fibrosis.
Within mouse and rat models of pulmonary induced fibrosis, lung spheroid cell secretome (LSC-Sec) and lung spheroid cell exosomes (LSC-Exo) were tested against commonly used mesenchymal stem cells. The therapeutics were delivered through a nebuliser allowing for the molecules to be inhaled directly into the lungs. Results demonstrated that inhalation treatment with either LSC-Exo or LSC-Sec promoted improvements compared to the control group. Furthermore, LSC-Sec resulted in an approximately 50.0% reduction of fibrosis compared with mesenchymal stem cell secretome treatment (32.4%) in one of the models of pulmonary fibrosis. Similar results were achieved in the rat model; furthermore, the study revealed that while LSC-Exo inhalation treatment alone can induce therapeutic effects similar to LSC-Sec treatment, the full secretome exerted the most therapeutic benefits.
The study holds great potential for future therapeutics, paving the way towards a noninvasive and cost-effective method of treating damaged lungs. Prof Cheng stated: “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.” The findings here indicate that products released from stem cells can be as effective as the stem cells themselves and may have implications in many other diseases utilising stem cell therapy. The team aims to expand the test into more pulmonary diseases such as acute respiratory distress syndrome, pulmonary hypertension, and chronic obstructive pulmonary disease.