Journal
RESPIROLOGY
Volume 26, Issue 2, Pages 161-170Publisher
WILEY
DOI: 10.1111/resp.13928
Keywords
bleomycin; cell-based therapy; lung fibrosis; mesenchymal stem cells; pulmonary
Categories
Funding
- Marcus Foundation
- Lester Smith Medical Research Institute
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This study investigates the effectiveness of MSC derived from different sources in treating lung fibrosis, finding that different sources may have varying effects on repair pathways in the body.
Background and objective IPF is a fatal and debilitating lung disorder increasing in incidence worldwide. To date, two approved treatments only slow disease progression, have multiple side effects and do not provide a cure. MSC have promising therapeutic potential as a cell-based therapy for many lung disorders based on the anti-fibrotic properties of the MSC. Methods Critical questions remain surrounding the optimal source, timing and efficacy of cell-based therapies. The present study examines the most effective sources of MSC. Human MSC were derived from adipose, WJ, chorionic membrane (CSC) and chorionic villi (CVC). MSC were injected into the ageing mouse model of BLM-induced lung fibrosis. Results All sources decreased Aschroft and hydroxyproline levels when injected into BLM-treated mice at day 10 with the exception of CSC cells that did not change hydroxyproline levels. There were also decreases in mRNA expression of alpha(v)-integrin and TNF alpha in all sources except CSC. Only ASC- and WJ-derived cells reduced AKT and MMP-2 activation, while Cav-1 was increased by ASC treatment as previously reported. BLM-induced miR dysregulation of miR-29 and miR-199 was restored only by ASC treatment. Conclusion Our data suggest that sources of MSC may differ in the pathway(s) involved in repair.
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