Fibrosis Development in HOCl-Induced Systemic Sclerosis: A Multistage Process Hampered by Mesenchymal Stem Cells.

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License: CC BY 4.0
Serval ID
serval:BIB_B10472CA6C87
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Fibrosis Development in HOCl-Induced Systemic Sclerosis: A Multistage Process Hampered by Mesenchymal Stem Cells.
Journal
Frontiers in immunology
Author(s)
Maria ATJ, Toupet K., Maumus M., Rozier P., Vozenin M.C., Le Quellec A., Jorgensen C., Noël D., Guilpain P.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
9
Pages
2571
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
<b>Objectives:</b> Skin fibrosis is the hallmark of systemic sclerosis (SSc) a rare intractable disease with unmet medical need. We previously reported the anti-fibrotic potential of mesenchymal stem cells (MSCs) in a murine model of SSc. This model, based on daily intra-dermal injections of hypochlorite (HOCl) during 6 weeks, is an inducible model of the disease. Herein, we aimed at characterizing the development of skin fibrosis in HOCl-induced SSc (HOCl-SSc), and evaluating the impact of MSC infusion during the fibrogenesis process. <b>Methods:</b> After HOCl-SSc induction in BALB/c mice, clinical, histological and biological parameters were measured after 3 weeks (d21) and 6 weeks (d42) of HOCl challenge, and 3 weeks after HOCl discontinuation (d63). Treated-mice received infusions of 2.5 × 10 <sup>5</sup> MSCs 3 weeks before sacrifice (d0, d21, d42). <b>Results:</b> HOCl injections induced a two-step process of fibrosis development: first, an 'early inflammatory phase', characterized at d21 by highly proliferative infiltrates of myofibroblasts, T-lymphocytes and macrophages. Second, a phase of 'established matrix fibrosis', characterized at d42 by less inflammation, but strong collagen deposition and followed by a third phase of 'spontaneous tissue remodeling' after HOCl discontinuation. This phase was characterized by partial fibrosis receding, due to enhanced MMP1/TIMP1 balance. MSC treatment reduced skin thickness in the three phases of fibrogenesis, exerting more specialized mechanisms: immunosuppression, abrogation of myofibroblast activation, or further enhancing tissue remodeling, depending on the injection time-point. <b>Conclusion:</b> HOCl-SSc mimics three fibrotic phenotypes of scleroderma, all positively impacted by MSC therapy, demonstrating the great plasticity of MSC, a promising cure for SSc.
Keywords
autoimmunity, cell therapy, fibrosis, hypochlorite, mesenchymal stem cells, oxidative stress, scleroderma, systemic sclerosis
Pubmed
Web of science
Open Access
Yes
Create date
19/11/2018 17:13
Last modification date
20/08/2019 15:20
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