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

Détails

Ressource 1Télécharger: 30455706_BIB_B10472CA6C87.pdf (14607.04 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_B10472CA6C87
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Fibrosis Development in HOCl-Induced Systemic Sclerosis: A Multistage Process Hampered by Mesenchymal Stem Cells.
Périodique
Frontiers in immunology
Auteur(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
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
9
Pages
2571
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
<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.
Mots-clé
autoimmunity, cell therapy, fibrosis, hypochlorite, mesenchymal stem cells, oxidative stress, scleroderma, systemic sclerosis
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/11/2018 17:13
Dernière modification de la notice
20/08/2019 15:20
Données d'usage