Mesenchymal stem cells attenuate inflammatory processes in the heart and lung via inhibition of TNF signaling

Alessandra Martire, Fikru B. Bedada, Shizuka Uchida, Jochen Pöling, Marcus Krüger, Henning Warnecke, Manfred Richter, Thomas Kubin, Susanne Herold, Thomas Braun

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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 NFκBp65 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 NFκBp65 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.

Original languageEnglish (US)
Article number54
JournalBasic research in cardiology
Volume111
Issue number5
DOIs
StatePublished - Sep 1 2016

Bibliographical note

Funding Information:
Open access funding provided by Max Planck Society. The authors wish to thank Sonja Krüger, Kerstin Richter, Ursula Hofmann, and Jutta Wetzel for excellent technical assistance. This work was supported by the Max-Planck-Society, the Leducq Foundation, the Excellence Initiative “Cardiopulmonary System”, the DFG (LO-271/4-2), the German Center for Lung Research and the German Center for Cardiovascular Research.

Publisher Copyright:
© 2016, The Author(s).

Keywords

  • Acute lung injury
  • Fibrosis
  • Heart failure
  • Inflammation
  • Mesenchymal stem cells
  • Proteomics
  • TNF-α

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