PMID- 23767885 OWN - NLM STAT- MEDLINE DCOM- 20140512 LR - 20181202 IS - 1557-8534 (Electronic) IS - 1547-3287 (Linking) VI - 22 IP - 21 DP - 2013 Nov 1 TI - Mesenchymal stem cells induce an inflammatory response after intravenous infusion. PG - 2825-35 LID - 10.1089/scd.2013.0193 [doi] AB - 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-beta, and TNF-alpha 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-alpha mRNA levels peaked 4 h after MSC infusion. The expression of the anti-inflammatory cytokines TGF-beta, 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. FAU - Hoogduijn, Martin J AU - Hoogduijn MJ AD - 1 Nephrology and Transplantation, Department of Internal Medicine, Erasmus Medical Center , Rotterdam, The Netherlands . FAU - Roemeling-van Rhijn, Marieke AU - Roemeling-van Rhijn M FAU - Engela, Anja U AU - Engela AU FAU - Korevaar, Sander S AU - Korevaar SS FAU - Mensah, Fane K F AU - Mensah FK FAU - Franquesa, Marcella AU - Franquesa M FAU - de Bruin, Ron W F AU - de Bruin RW FAU - Betjes, Michiel G H AU - Betjes MG FAU - Weimar, Willem AU - Weimar W FAU - Baan, Carla C AU - Baan CC LA - eng PT - Journal Article DEP - 20130809 PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Lipopolysaccharides) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Adipose Tissue/cytology MH - Animals MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Chemokines/blood/genetics/*immunology MH - Cytokines/blood/genetics/*immunology MH - Gene Expression/immunology MH - Green Fluorescent Proteins/genetics/metabolism MH - Inflammation Mediators/blood/immunology/metabolism MH - Infusions, Intravenous MH - Kidney/immunology/metabolism MH - Lipopolysaccharides/immunology/pharmacology MH - Liver/immunology/metabolism MH - Lung/*immunology/metabolism MH - Macrophages/immunology/metabolism MH - Male MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/*immunology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Reverse Transcriptase Polymerase Chain Reaction MH - Spleen/cytology/drug effects/immunology MH - Time Factors EDAT- 2013/06/19 06:00 MHDA- 2014/05/13 06:00 CRDT- 2013/06/18 06:00 PHST- 2013/06/18 06:00 [entrez] PHST- 2013/06/19 06:00 [pubmed] PHST- 2014/05/13 06:00 [medline] AID - 10.1089/scd.2013.0193 [doi] PST - ppublish SO - Stem Cells Dev. 2013 Nov 1;22(21):2825-35. doi: 10.1089/scd.2013.0193. Epub 2013 Aug 9.