Journal article

Publication year: 2016

Journal: Basic Research in Cardiology

Volume number: 111

Issue number: 5

ISSN: 0300-8428

eISSN: 1435-1803

Open access status: Hybrid

DOI Link: https://doi.org/10.1007/s00395-016-0573-2

Publisher: Springer

Abstract: 
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.

Harvard Citation style: Martire, A., Bedada, F., Uchida, S., Poeling, J., Krueger, M., Warnecke, H., et al. (2016) Mesenchymal stem cells attenuate inflammatory processes in the heart and lung via inhibition of TNF signaling, Basic Research in Cardiology, 111(5), Article 54. https://doi.org/10.1007/s00395-016-0573-2

APA Citation style: Martire, A., Bedada, F., Uchida, S., Poeling, J., Krueger, M., Warnecke, H., Richter, M., Kubin, T., Herold, S., & Braun, T. (2016). Mesenchymal stem cells attenuate inflammatory processes in the heart and lung via inhibition of TNF signaling. Basic Research in Cardiology. 111(5), Article 54. https://doi.org/10.1007/s00395-016-0573-2