title: Mesenchymal stem cells induce an inflammatory response after intravenous infusion.
abstract: Mesenchymal stem cells (MSCs) have potent immunosuppressive effects in vitro and are considered as a therapeutic option for autoimmune disease and organ transplantation. While MSCs show beneficial effects on immune disease progression and transplant survival in animal models, the immunomodulatory mechanisms involved are largely unknown. In the present study, we show that intravenously infused C57BL/6- green fluorescent protein (GFP) MSCs home to the lungs in C57BL/6 recipient mice and induce an inflammatory response. This response was characterized by increased mRNA expression of monocyte chemoattractant protein-1 (MCP1), IL1-β, and TNF-α and an increase in macrophages in lung tissue 2 h after MSC infusion. Simultaneously, serum levels of proinflammatory IL6, CXCL1, and MCP1 protein increased, demonstrating systemic immune activation after MSC infusion. In liver tissue, no C57BL/6-GFP MSCs were detected, but MCP1 and TNF-α mRNA levels peaked 4 h after MSC infusion. The expression of the anti-inflammatory cytokines TGF-β, IL4, and IL10 was only marginally affected. Nevertheless, 3 days after MSC infusion, animals developed a milder inflammatory response to lipopolysaccharides. Our results suggest that the in vivo immunomodulatory effects of MSCs originate from an inflammatory response that is induced by the infusion of MSCs, which is followed by a phase of reduced immune reactivity.
authors.affiliation: 1 Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center , Rotterdam, The Netherlands .
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hoogduijn
authors.forename: Marieke
authors.initials: M
authors.lastname: Roemeling-van Rhijn
authors.forename: Anja U
authors.initials: AU
authors.lastname: Engela
authors.forename: Sander S
authors.initials: SS
authors.lastname: Korevaar
authors.forename: Fane K F
authors.initials: FK
authors.lastname: Mensah
authors.forename: Marcella
authors.initials: M
authors.lastname: Franquesa
authors.forename: Ron W F
authors.initials: RW
authors.lastname: de Bruin
authors.forename: Michiel G H
authors.initials: MG
authors.lastname: Betjes
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000097:blood / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood / Q000276:immunology / Q000378:metabolism; D007262:Infusions, Intravenous; D007668:Kidney / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
chemical_list: D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D049452:Green Fluorescent Proteins