期刊
BASIC RESEARCH IN CARDIOLOGY
卷 111, 期 5, 页码 -出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00395-016-0573-2
关键词
Mesenchymal stem cells; Proteomics; TNF-alpha; Fibrosis; Inflammation; Heart failure; Acute lung injury
资金
- Max Planck Society
- Leducq Foundation
- Excellence Initiative Cardiopulmonary System
- DFG [LO-271/4-2]
- German Center for Lung Research
- German Center for Cardiovascular Research
Mesenchymal stem cells ( MSC) have been used to treat different clinical conditions although the mechanisms by which pathogenetic processes are affected are still poorly understood. We have previously analyzed the homing of bone marrow-derived MSC to diseased tissues characterized by a high degree of mononuclear cell infiltration and postulated that MSC might modulate inflammatory responses. Here, we demonstrate that MSC mitigate adverse tissue remodeling, improve organ function, and extend lifespan in a mouse model of inflammatory dilative cardiomyopathy ( DCM). Furthermore, MSC attenuate Lipopolysaccharide-induced acute lung injury indicating a general role in the suppression of inflammatory processes. We found that MSC released sTNF-RI, which suppressed activation of the NFjBp65 pathway in cardiomyocytes during DCM in vivo. Substitution of MSC by recombinant soluble TNF-R partially recapitulated the beneficial effects of MSC while knockdown of TNF-R prevented MSC-mediated suppression of the NFjBp65 pathway and improvement of tissue pathology. We conclude that sTNF-RI is a major part of the paracrine machinery by which MSC effect local inflammatory reactions.
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