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Stem Cells. 2016 Sep;34(9):2393-406. doi: 10.1002/stem.2417. Epub 2016 Jun 27.

Suppression of Neutrophil-Mediated Tissue Damage-A Novel Skill of Mesenchymal Stem Cells.

Author information

1
Department of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany.
2
Department of Biochemistry, School of Medicine, Justus-Liebig-University of Giessen, Giessen, Germany.
3
Ticeba GmbH, Heidelberg, Germany.
4
Department of Medicine, Boston VA Healthcare System, West Roxbury, Massachusetts, USA.
5
Division of Genetics, Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
6
Transplant Research Program, Boston Children's Hospital, Boston, Massachusetts, USA.
7
Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
8
School of Medical Sciences, Edith Cowan University, Joondalup, WA, Australia.
9
Department of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany. karin.scharffetter-kochanek@uniklinik-ulm.de.

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. Stem Cells 2016;34:2393-2406.

KEYWORDS:

Mesenchymal stem cells; Neutrophil extracellular traps; Neutrophils; Superoxide dismutase; Vasculitis

PMID:
27299700
PMCID:
PMC5572139
DOI:
10.1002/stem.2417
[Indexed for MEDLINE]
Free PMC Article

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