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Reactive bone marrow stromal cells attenuate systemic inflammation via sTNFR1
Hiroshi Yagi1, Alejandro Soto-Gutierrez, Nalu Navarro-Alvarez
1Department of Surgery, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospitals for Children, Boston, Massachusetts, USA.
Summary
Mesenchymal stem cells (MSCs) reduce inflammation by secreting soluble tumor necrosis factor receptor 1 (sTNFR1). This mechanism, dependent on nuclear factor kappa B (NFκB) activation, helps protect organs from inflammatory damage in animal models.
Area of Science:
- Immunology
- Cell Biology
- Regenerative Medicine
Background:
- Systemic inflammation post-trauma, sepsis, or burns can cause organ damage.
- Mesenchymal stem cells (MSCs) show potential in treating immune disorders by modulating inflammation.
- The precise mechanisms by which MSCs exert their anti-inflammatory effects require further elucidation.
Purpose of the Study:
- To investigate the hypothesis that MSCs secrete factors that neutralize inflammatory cytokines.
- To identify specific factors secreted by MSCs in response to inflammatory stimuli.
- To determine the role of nuclear factor kappa B (NFκB) in MSC-mediated anti-inflammatory responses.
Main Methods:
- Co-culture of MSCs with epithelial cells in inflammatory serum conditions.
- Proteomic screening to identify secreted factors.
- Inhibition of NFκB activation in MSCs.
- Intramuscular transplantation of MSCs in lipopolysaccharide (LPS)-endotoxic rat models.
Main Results:
- Co-cultured MSCs decreased NFκB activation in epithelial cells.
- Proteomic analysis identified soluble tumor necrosis factor receptor 1 (sTNFR1) secretion by MSCs exposed to LPS-stimulated serum.
- NFκB inhibition abolished the responsive secretion of sTNFR1.
- MSC transplantation reduced inflammatory cytokines and immune cell infiltration in multiple organs.
Conclusions:
- MSCs decrease NFκB activation in target cells during inflammation.
- NFκB-dependent secretion of sTNFR1 by MSCs is a key mechanism for modulating inflammatory responses.
- These findings suggest MSCs can protect organs from inflammatory damage through specific secreted factors.
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