title: The immunosuppressive signature of menstrual blood mesenchymal stem cells entails opposite effects on experimental arthritis and graft versus host diseases.
abstract: Recently, a noninvasive and highly proliferative stem cell population from menstrual blood called MenSCs has been identified. Despite their use in clinical studies, their immunomodulatory properties have not yet been investigated. In this context, we studied the immunosuppressive properties of MenSCs in comparison with the well-characterized bone marrow derived-MSCs (BM-MSCs). Using an in vitro proliferation assays, we showed that MenSCs displayed a lower suppressive effect on peripheral blood mononuclear cells and in particular on the proinflammatory CD4(+) IFN-γ(+) and CD8(+) IFNγ(+) cells than BM-MSCs. Moreover, compared to BM-MSCs, MenSCs activated with IFN-γ and IL-1β produced lower amounts of immunosuppressive factors such as IDO, PDL-1, PGE2, and Activin A and exhibited a substantial lower expression level of IFN-γ receptor subunits. In the collagen induced arthritis model, while BM-MSCs administration resulted in a potent therapeutic effect associated with a significant decrease of proinflammatory T cell frequency in the lymph nodes, MenSCs injection did not. In contrast, in the xeno-GVHD model, only MenSCs administration significantly increased the survival of mice. This beneficial effect mediated by MenSCs was associated with a higher capacity to migrate into the intestine and liver and not to their anti-inflammatory capacities. All together our results demonstrate for the first time that the therapeutic potential of MSC in the experimental xeno-GVHD model is independent of their immunosuppressive properties. These findings should be taken into consideration for the development of safe and effective cell therapies.
authors.affiliation: Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.|Inserm, U1183, Montpellier, France.|University Montpellier, Montpellier, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Luz-Crawford
authors.affiliation: Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Torres
authors.affiliation: Inserm, U1183, Montpellier, France.|University Montpellier, Montpellier, France.
authors.forename: Daniele
authors.initials: D
authors.lastname: Noël
authors.affiliation: Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.|Cells for Cells, Santiago, Chile.
authors.forename: Ainoa
authors.initials: A
authors.lastname: Fernandez
authors.affiliation: Inserm, U1183, Montpellier, France.|University Montpellier, Montpellier, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Toupet
authors.affiliation: Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.|Cells for Cells, Santiago, Chile.
authors.forename: Francisca
authors.initials: F
authors.lastname: Alcayaga-Miranda
authors.affiliation: Inserm, U1183, Montpellier, France.|University Montpellier, Montpellier, France.
authors.forename: Gautier
authors.initials: G
authors.lastname: Tejedor
authors.affiliation: Inserm, U1183, Montpellier, France.|University Montpellier, Montpellier, France.|Clinical Immunology and Osteoarticular Diseases Therapeutic Unit, Lapeyronie University Hospital, Montpellier, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Jorgensen
authors.affiliation: Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Illanes
authors.affiliation: Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.
authors.forename: Fernando E
authors.initials: FE
authors.lastname: Figueroa
authors.affiliation: Inserm, U1183, Montpellier, France.|University Montpellier, Montpellier, France.
authors.forename: Farida
authors.initials: F
authors.lastname: Djouad
authors.affiliation: Laboratory of Nano-Regenerative Medicine, Faculty of Medicine, Universidad de Los Andes, Santiago, Chile.|Cells for Cells, Santiago, Chile.
authors.forename: Maroun
authors.initials: M
authors.lastname: Khoury
mesh_terms: D000293:Adolescent; D000328:Adult; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D064593:Heterografts; D006801:Humans; D008297:Male; D008597:Menstrual Cycle; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D008875:Middle Aged; D023001:Transplantation Tolerance
keywords: CIA; GVHD; Immunosuppression; Menstrual-blood derived MSCs