Back to Search Start Over

Induced pluripotent stem cell-derived mesenchymal stem cells reverse bleomycin-induced pulmonary fibrosis and related lung stiffness.

Authors :
Chakraborty A
Wang C
Hodgson-Garms M
Broughton BRS
Frith JE
Kelly K
Samuel CS
Source :
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Sep; Vol. 178, pp. 117259. Date of Electronic Publication: 2024 Aug 07.
Publication Year :
2024

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.)

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