Adipose-derived mesenchymal stromal/stem cells in systemic sclerosis: Alterations in function and beneficial effect on lung fibrosis are regulated by caveolin-1. Issue 2 (June 2019)

• Record Type: Journal Article
• Authors: Lee, Rebecca; Del Papa, Nicoletta; Introna, Martin; Reese, Charles F; Zemskova, Marina; Bonner, Michael; Carmen-Lopez, Gustavo; Helke, Kristi; Hoffman, Stanley; Tourkina, Elena
• Is Part Of: Journal of scleroderma and related disorders. Volume 4:Issue 2(2019)
• Page Start: 127
• Page End: 136
• Publication Date: 2019-06
• Subjects: Caveolin-1 -- fibrosis -- adipogenesis -- mesenchymal stem cells -- scleroderma; Scleroderma (Disease) -- Periodicals; Systemic scleroderma -- Periodicals; Fibrosis -- Periodicals; 616.544
• DOI: 10.1177/2397198318821510
• Languages: English
• ISSNs: 2397-1983

Abstract

The potential value of mesenchymal stromal/stem cell therapy in treating skin fibrosis in scleroderma (systemic sclerosis) and of the caveolin-1 scaffolding domain peptide in treating lung, skin, and heart fibrosis is known. To understand how these observations may relate to differences between mesenchymal stromal/stem cells from healthy subjects and subjects with fibrosis, we have characterized the fibrogenic and adipogenic potential of adipose-derived mesenchymal stromal/stem cells from systemic sclerosis patients, from mice with fibrotic lung and skin disease induced by systemic bleomycin treatment, and from healthy controls. Early passage systemic sclerosis adipose-derived mesenchymal stromal/stem cells have a profibrotic/anti-adipogenic phenotype compared to healthy adipose-derived mesenchymal stromal/stem cells (low caveolin-1, high α-smooth muscle actin, high HSP47, low pAKT, low capacity for adipogenic differentiation). This phenotype is mimicked by treating healthy adipose-derived mesenchymal stromal/stem cells with transforming growth factor beta or caveolin-1 small interfering RNA and is reversed in systemic sclerosis adipose-derived mesenchymal stromal/stem cells by treatment with caveolin-1 scaffolding domain peptide, but not scrambled caveolin-1 scaffolding domain peptide. Similar results were obtained with adipose-derived mesenchymal stromal/stem cells from systemic sclerosis patients and from bleomycin-treated mice, indicating the central role of caveolin-1 in mesenchymal stromal/stem cell differentiation in fibrotic disease.