title: Human adipose mesenchymal stem cells as potent anti-fibrosis therapy for systemic sclerosis.
abstract: Displaying immunosuppressive and trophic properties, mesenchymal stem/stromal cells (MSC) are being evaluated as promising therapeutic options in a variety of autoimmune and degenerative diseases. Although benefits may be expected in systemic sclerosis (SSc), a rare autoimmune disease with fibrosis-related mortality, MSC have yet to be evaluated in this specific condition. While autologous approaches could be inappropriate because of functional alterations in MSC from patients, the objective of the present study was to evaluate allogeneic and xenogeneic MSC in the HOCl-induced model of diffuse SSc. We also questioned the source of human MSC and compared bone marrow- (hBM-MSC) and adipose-derived MSC (hASC).
  
  
  
  HOCl-challenged BALB/c mice received intravenous injection of BM-MSC from syngeneic BALB/c or allogeneic C57BL/6 mice, and xenogeneic hBM-MSC or hASC (3 donors each). Skin thickness was measured during the experiment. At euthanasia, histology, immunostaining, collagen determination and RT-qPCR were performed in skin and lungs.
  
  
  
  Xenogeneic hBM-MSC were as effective as allogeneic or syngeneic BM-MSC in decreasing skin thickness, expression of Col1, Col3, α-Sma transcripts, and collagen content in skin and lungs. This anti-fibrotic effect was not associated with MSC migration to injured skin or with long-term MSC survival. Interestingly, compared with hBM-MSC, hASC were significantly more efficient in reducing skin fibrosis, which was related to a stronger reduction of TNFα, IL1β, and enhanced ratio of Mmp1/Timp1 in skin and lung tissues.
  
  
  
  Using primary cells isolated from 3 murine and 6 human individuals, this preclinical study demonstrated similar therapeutic effects using allogeneic or xenogeneic BM-MSC while ASC exerted potent anti-inflammatory and remodeling properties. This sets the proof-of-concept prompting to evaluate the therapeutic efficacy of allogeneic ASC in SSc patients.
authors.affiliation: Inserm, U 1183, Saint-Eloi Hospital, 80 ave Augustin Fliche, Montpellier, F-34295, France; Montpellier University, Medical School, 2 rue de l'Ecole de Médecine, Montpellier, F-34967, France; Department of Internal Medicine, Multiorganic Diseases, Saint-Eloi Hospital, 80 ave Augustin Fliche, Montpellier, F-34295, France.
authors.forename: Alexandre T J
authors.initials: AT
authors.lastname: Maria
authors.affiliation: Inserm, U 1183, Saint-Eloi Hospital, 80 ave Augustin Fliche, Montpellier, F-34295, France; Montpellier University, Medical School, 2 rue de l'Ecole de Médecine, Montpellier, F-34967, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Toupet
authors.affiliation: Inserm, U 1183, Saint-Eloi Hospital, 80 ave Augustin Fliche, Montpellier, F-34295, France; Montpellier University, Medical School, 2 rue de l'Ecole de Médecine, Montpellier, F-34967, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Maumus
authors.affiliation: Inserm, U 1183, Saint-Eloi Hospital, 80 ave Augustin Fliche, Montpellier, F-34295, France; Montpellier University, Medical School, 2 rue de l'Ecole de Médecine, Montpellier, F-34967, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Fonteneau
authors.affiliation: Montpellier University, Medical School, 2 rue de l'Ecole de Médecine, Montpellier, F-34967, France; Department of Internal Medicine, Multiorganic Diseases, Saint-Eloi Hospital, 80 ave Augustin Fliche, Montpellier, F-34295, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Le Quellec
authors.affiliation: Inserm, U 1183, Saint-Eloi Hospital, 80 ave Augustin Fliche, Montpellier, F-34295, France; Montpellier University, Medical School, 2 rue de l'Ecole de Médecine, Montpellier, F-34967, France; Clinical Unit for Osteoarticular Diseases and Department for Biotherapy, Lapeyronie Hospital, ave du Doyen Giraud, Montpellier, F-34295, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.affiliation: Inserm, U 1183, Saint-Eloi Hospital, 80 ave Augustin Fliche, Montpellier, F-34295, France; Montpellier University, Medical School, 2 rue de l'Ecole de Médecine, Montpellier, F-34967, France; Department of Internal Medicine, Multiorganic Diseases, Saint-Eloi Hospital, 80 ave Augustin Fliche, Montpellier, F-34295, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Guilpain
authors.affiliation: Inserm, U 1183, Saint-Eloi Hospital, 80 ave Augustin Fliche, Montpellier, F-34295, France; Montpellier University, Medical School, 2 rue de l'Ecole de Médecine, Montpellier, F-34967, France; Clinical Unit for Osteoarticular Diseases and Department for Biotherapy, Lapeyronie Hospital, ave du Doyen Giraud, Montpellier, F-34295, France. Electronic address: daniele.noel@inserm.fr.
authors.forename: Danièle
authors.initials: D
authors.lastname: Noël
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015415:Biomarkers; D018929:Cell Culture Techniques; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005355:Fibrosis; D015870:Gene Expression; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D012595:Scleroderma, Systemic / Q000209:etiology / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D012867:Skin / Q000378:metabolism / Q000473:pathology
chemical_list: D015415:Biomarkers
keywords: Adipose stem cells; Fibrosis; Mesenchymal stem cells; Systemic sclerosis