4.7 Article

Anti-Inflammatory and Anti-Fibrotic Effect of Immortalized Mesenchymal-Stem-Cell-Derived Conditioned Medium on Human Lung Myofibroblasts and Epithelial Cells

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MDPI
DOI: 10.3390/ijms23094570

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ADSCs; mesenchymal stem cells; conditioned medium; pulmonary subepithelial myofibroblasts; A549; idiopathic pulmonary fibrosis; fibrosis; inflammation

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Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no known effective treatment. Researchers have found that conditioned media (CM) from an immortalized human adipose mesenchymal stem cell line can have anti-inflammatory and anti-fibrotic effects on pulmonary cells. CM reduces the production of chemokines and collagen Type III, and inhibits the migration of myofibroblasts.
Idiopathic pulmonary fibrosis (IPF) is caused by progressive lung tissue impairment due to extended chronic fibrosis, and it has no known effective treatment. The use of conditioned media (CM) from an immortalized human adipose mesenchymal stem cell line could be a promising therapeutic strategy, as it can reduce both fibrotic and inflammatory responses. We aimed to investigate the anti-inflammatory and anti-fibrotic effect of CM on human pulmonary subepithelial myofibroblasts (hPSM) and on A549 pulmonary epithelial cells, treated with pro-inflammatory or pro-fibrotic mediators. CM inhibited the proinflammatory cytokine-induced mRNA and protein production of various chemokines in both hPSMs and A549 cells. It also downregulated the mRNA expression of IL-1 alpha, but upregulated IL-1 beta and IL-6 mRNA production in both cell types. CM downregulated the pro-fibrotic-induced mRNA expression of collagen Type III and the migration rate of hPSMs, but upregulated fibronectin mRNA production and the total protein collagen secretion. CM's direct effect on the chemotaxis and cell recruitment of immune-associated cells, and its indirect effect on fibrosis through the significant decrease in the migration capacity of hPSMs, makes it a plausible candidate for further development towards a therapeutic treatment for IPF.

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