Fibrosis Development in HOCl-Induced Systemic Sclerosis: A Multistage Process Hampered by Mesenchymal Stem Cells.
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2018
- doi: 10.3389/fimmu.2018.02571
- issn: 1664-3224
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info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.02571
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info:eu-repo/semantics/altIdentifier/pmid/30455706
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info:eu-repo/semantics/altIdentifier/eissn/1664-3224
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_B10472CA6C870
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
Sujets proches
Scleroderma, Systemic Systemic sclerosis Progressive systemic sclerosis Sclerosis, Progressive systemic Integument (Skin) Cutis Service of process Service of papers Abuse of process Process Pattern Model Stromal cells, Marrow Stromal cells, Bone marrow Bone marrow stromal cells Marrow stromal cells MSCs (Mesenchymal stem cells)Citer ce document
ATJ Maria et al., « Fibrosis Development in HOCl-Induced Systemic Sclerosis: A Multistage Process Hampered by Mesenchymal Stem Cells. », Serveur académique Lausannois, ID : 10.3389/fimmu.2018.02571
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Objectives: 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. Methods: 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 5 MSCs 3 weeks before sacrifice (d0, d21, d42). Results: 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. Conclusion: 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.