Reactive bone marrow stromal cells attenuate systemic inflammation via sTNFR1

Hiroshi Yagi, Alejandro Soto-Gutierrez*, Nalu Navarro-Alvarez, Yaakov Nahmias, Yoni Goldwasser, Yuko Kitagawa, Arno W. Tilles, Ronald G. Tompkins, Biju Parekkadan, Martin L. Yarmush

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

140 Scopus citations


Excessive systemic inflammation following trauma, sepsis, or burn could lead to distant organ damage. The transplantation of bone marrow stromal cells or mesenchymal stem cells (MSCs) has been reported to be an effective treatment for several immune disorders by modulating the inflammatory response to injury. We hypothesized that MSCs can dynamically secrete systemic factors that can neutralize the activity of inflammatory cytokines. In this study, we showed that cocultured MSCs are able to decrease nuclear factor -B (NFB) activation in target epithelial cells incubated in inflammatory serum conditions. Proteomic screening revealed a responsive secretion of soluble tumor necrosis factor (TNF) receptor 1 (sTNFR1) when MSCs were exposed to lipopolysaccharide (LPS)-stimulated rat serum. The responsive effect was eliminated when NFB activation was blocked in MSCs. Intramuscular transplantation of MSCs in LPS-endotoxic rats decreased a panel of inflammatory cytokines and inflammatory infiltration of macrophages and neutrophils in lung, kidney, and liver when compared to controls. These results suggest that improvements of inflammatory responses in animal models after local transplantation of MSCs are at least, in part, explained by the NFB-dependent secretion of sTNFR1 by MSCs.

Original languageAmerican English
Pages (from-to)1857-1864
Number of pages8
JournalMolecular Therapy
Issue number10
StatePublished - Oct 2010

Bibliographical note

Funding Information:
We acknowledge the technical assistance of Bob Crowther for preparing histological samples. This work was supported by grants from the National Institutes of Health (1K99DK083556-01 to A.S.-G., 5R01DK059766-06 to M.L.Y.), the Broad Medical Research Foundation (BMRP498382 to B.P.), the Shriners Hospitals for Children and the American Liver Foundation support to A.S.-G. All authors have no conflict of interest.


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