Muscle Derived Mesenchymal Stem Cells Inhibit the Activity of the Free and the Neutrophil Extracellular Trap (NET)-Bond Myeloperoxidase.

Thierry Franck,Didier Serteyn,Hélène Graide,Justine Ceusters,Ange Mouithys-Mickalad

doi:10.3390/cells10123486

Abstract

Mesenchymal stem cells (MSCs) are known to migrate to tissue injury sites to participate in immune modulation, tissue remodelling and wound healing, reducing tissue damage. Upon neutrophil activation, there is a release of myeloperoxidase (MPO), an oxidant enzyme. But little is known about the direct role of MSCs on MPO activity. The aim of this study was to investigate the effect of equine mesenchymal stem cells derived from muscle microinvasive biopsy (mdMSC) on the oxidant response of neutrophils and particularly on the activity of the myeloperoxidase released by stimulated equine neutrophils. After specific treatment (trypsin and washings in phosphate buffer saline), the mdMSCs were exposed to isolated neutrophils. The effect of the suspended mdMSCs was studied on the ROS production and the release of total and active MPO by stimulated neutrophils and specifically on the activity of MPO in a neutrophil-free model. Additionally, we developed a model combining adherent mdMSCs with neutrophils to study total and active MPO from the neutrophil extracellular trap (NET). Our results show that mdMSCs inhibited the ROS production, the activity of MPO released by stimulated neutrophils and the activity of MPO bound to the NET. Moreover, the co-incubation of mdMSCs directly with MPO results in a strong inhibition of the peroxidase activity of MPO, probably by affecting the active site of the enzyme. We confirm the strong potential of mdMSCs to lower the oxidant response of neutrophils. The novelty of our study is an evident inhibition of the activity of MPO by MSCs. The results indicated a new potential therapeutic approach of mdMSCs in the inhibition of MPO, which is considered as a pro-oxidant actor in numerous chronic and acute inflammatory pathologies.

Highlights

Introduction iationsIn addition to their well-known regenerative properties, mesenchymal stem cells (MSCs) exhibit anti-inflammatory properties which have led to their increasing therapeutic use [1,2]
The data were obtained from 5 independent experiments performed with different neutrophils and Muscle-Derived Mesenchymal Stem Cells (mdMSC) preparations
For total MPO, the stimulation of PMNs with CB/fMLP inUsing the SIEFED technique, we showed that mdMSCS induce a strong dose dependuced a moderate but significant (* p < 0.05) release of MPO compared to non-stimulated dent inhibition of purified MPO activity in a neutrophil-free system (Figure 3)

Summary

Introduction

In addition to their well-known regenerative properties, mesenchymal stem cells (MSCs) exhibit anti-inflammatory properties which have led to their increasing therapeutic use [1,2]. MSCs are known to migrate to tissue damage sites, where they participate in tissue remodelling, wound healing and modulation of the immune response [3]. The paracrine activity appeared as a predominant mechanism by which MSCs participate in tissue repair instead of engraftment and differentiation into functional cells [4,5] and has been shown to decrease angiogenesis and apoptosis and to modulate extracellular matrix dynamics and inflammation [3]. MSCs influence the immune system through anti-inflammatory properties and modulate the activity and function of macrophages and neutrophils [6]. A recent study showed that modulation of the redox environment and oxidative stress by MSCs can Licensee MDPI, Basel, Switzerland

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