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Mesenchymal stem cells induce an inflammatory response after intravenous infusion.
- Source :
-
Stem cells and development [Stem Cells Dev] 2013 Nov 01; Vol. 22 (21), pp. 2825-35. Date of Electronic Publication: 2013 Aug 09. - Publication Year :
- 2013
-
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.
- Subjects :
- Adipose Tissue cytology
Animals
Cell Proliferation drug effects
Cells, Cultured
Chemokines blood
Chemokines genetics
Cytokines blood
Cytokines genetics
Gene Expression immunology
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Inflammation Mediators blood
Inflammation Mediators immunology
Inflammation Mediators metabolism
Infusions, Intravenous
Kidney immunology
Kidney metabolism
Lipopolysaccharides immunology
Lipopolysaccharides pharmacology
Liver immunology
Liver metabolism
Lung metabolism
Macrophages immunology
Macrophages metabolism
Male
Mesenchymal Stem Cells metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Reverse Transcriptase Polymerase Chain Reaction
Spleen cytology
Spleen drug effects
Spleen immunology
Time Factors
Chemokines immunology
Cytokines immunology
Lung immunology
Mesenchymal Stem Cell Transplantation methods
Mesenchymal Stem Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1557-8534
- Volume :
- 22
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Stem cells and development
- Publication Type :
- Academic Journal
- Accession number :
- 23767885
- Full Text :
- https://doi.org/10.1089/scd.2013.0193