Document Type
Journal Article
Publisher
Marsland Press
Place of Publication
United States
School
School of Medical and Health Sciences
RAS ID
24483
Funders
Baden-Württemberg Stiftung (P-BWS-ASII/15)
European Commission (CASCADE HEALTH-FP7-223236)
German Research Foundation (SFB1149)
Baustein Program from the Medical Faculty, University of Ulm (LSBN.0100)
Excellence Cluster Cardiopulmonary System (ECCPS)
Abstract
Mesenchymal stem cells (MSCs) are crucial for tissue homeostasis and regeneration. Though of prime interest, their potentially protective role on neutrophil-induced tissue damage, associated with high morbidity and mortality, has not been explored in sufficient detail. Here we report the therapeutic skill of MSCs to suppress unrestrained neutrophil activation and to attenuate severe tissue damage in a murine immune-complex mediated vasculitis model of unbalanced neutrophil activation. MSC-mediated neutrophil suppression was due to intercellular adhesion molecule 1-dependent engulfment of neutrophils by MSCs, decreasing overall neutrophil numbers. Similar to MSCs in their endogenous niche of murine and human vasculitis, therapeutically injected MSCs via upregulation of the extracellular superoxide dismutase (SOD3), reduced superoxide anion concentrations and consequently prevented neutrophil death, neutrophil extracellular trap formation and spillage of matrix degrading neutrophil elastase, gelatinase and myeloperoxidase. SOD3-silenced MSCs did not exert tissue protective effects. Thus, MSCs hold substantial therapeutic promise to counteract tissue damage in conditions with unrestrained neutrophil activation.
DOI
10.1002/stem.2417
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Comments
Jiang, D., Muschhammer, J., Qi, Y., Kügler, A., deVries, J., Saffarzadeh, M., ... Scharffetter_Kochanek, K. (2016). Suppression of neutrophil-mediated tissue damage— A novel skill of mesenchymal stem cells. Stem Cells, 34(9), 2393-2406.
https://doi.org/10.1002/stem.2417