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Induced pluripotent stem cell-derived mesenchymal stem cells reverse bleomycin-induced pulmonary fibrosis and related lung stiffness.
- Source :
-
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Sep; Vol. 178, pp. 117259. Date of Electronic Publication: 2024 Aug 07. - Publication Year :
- 2024
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Abstract
- Idiopathic pulmonary fibrosis (IPF) is characterised by lung scarring and stiffening, for which there is no effective cure. Based on the immunomodulatory and anti-fibrotic effects of induced pluripotent stem cell (iPSC) and mesenchymoangioblast-derived mesenchymal stem cells (iPSCs-MSCs), this study evaluated the therapeutic effects of iPSCs-MSCs in a bleomycin (BLM)-induced model of pulmonary fibrosis. Adult male C57BL/6 mice received a double administration of BLM (0.15 mg/day) 7-days apart and were then maintained for a further 28-days (until day-35), whilst control mice were administered saline 7-days apart and maintained for the same time-period. Sub-groups of BLM-injured mice were intravenously-injected with 1×10 <superscript>6</superscript> iPSC-MSCs on day-21 alone or on day-21 and day-28 and left until day-35 post-injury. Measures of lung inflammation, fibrosis and compliance were then evaluated. BLM-injured mice presented with lung inflammation characterised by increased immune cell infiltration and increased pro-inflammatory cytokine expression, epithelial damage, lung transforming growth factor (TGF)-β1 activity, myofibroblast differentiation, interstitial collagen fibre deposition and topology (fibrosis), in conjunction with reduced matrix metalloproteinase (MMP)-to-tissue inhibitor of metalloproteinase (TIMP) ratios and dynamic lung compliance. All these measures were ameliorated by a single or once-weekly intravenous-administration of iPSC-MSCs, with the latter reducing dendritic cell infiltration and lung epithelial damage, whilst promoting anti-inflammatory interleukin (IL)-10 levels to a greater extent. Proteomic profiling of the conditioned media of cultured iPSC-MSCs that were stimulated with TNF-α and IFN-γ, revealed that these stem cells secreted protein levels of immunosuppressive factors that contributed to the anti-fibrotic and therapeutic potential of iPSCs-MSCs as a novel treatment option for IPF.<br />Competing Interests: Declaration of Competing Interest All Authors have nothing to disclose.<br /> (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Subjects :
- Animals
Male
Mice
Cell Differentiation drug effects
Cytokines metabolism
Disease Models, Animal
Transforming Growth Factor beta1 metabolism
Bleomycin
Induced Pluripotent Stem Cells
Mice, Inbred C57BL
Mesenchymal Stem Cells metabolism
Pulmonary Fibrosis chemically induced
Pulmonary Fibrosis pathology
Pulmonary Fibrosis therapy
Lung pathology
Lung drug effects
Lung metabolism
Mesenchymal Stem Cell Transplantation methods
Subjects
Details
- Language :
- English
- ISSN :
- 1950-6007
- Volume :
- 178
- Database :
- MEDLINE
- Journal :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Publication Type :
- Academic Journal
- Accession number :
- 39116786
- Full Text :
- https://doi.org/10.1016/j.biopha.2024.117259