Abstract

The mesenchymal stem cells obtained from human amniotic membrane (hAMSC) possess immunosuppressive functions through soluble factors such as prostanoids and proteins; thus, they have been proposed to ameliorate inflammatory processes. On the other hand, activated neutrophils are cells of the first line of immune defense that are able to release extracellular traps (NETs). NETs are formed of DNA and granular components; however, the excessive release of NETs is associated with the development of autoimmune and chronic inflammatory diseases. In this study, we identified that conditioned medium (CM) from hAMSC was able to diminish NETs release, as well as the production of reactive oxygen species (ROS) and the mitochondrial membrane potential from LPS-stimulated mouse bone marrow-derived neutrophils (BMN). Interestingly, NETs inhibition, ROS levels decrease and mitochondrial membrane potential loss were reverted when LPS-stimulated murine derived BMN were exposed to the CM from hAMSC transfected with TSG-6-siRNA. Finally, rhTSG6 was able to significantly diminish NETs release in BMN. These data suggest an inhibition mechanism of NETs ROS-dependent in which TSG-6 participates. Consequently, we propose the hAMSC use as a therapeutic candidate in the treatment of inflammatory diseases in which NETs are involved.

Highlights

  • The human amniotic membrane[19]

  • According to the criteria proposed by the First International Workshop on Placenta Derived Stem Cells[47], these cells attached to plastic adopted a fibroblastoid shape (Fig. 1A, upper-left panel); they made colony-forming units as observed with the crystal violet staining (Fig. 1B, upper-right panel)

  • The cells obtained from the mesoderm of human amnion showed stem cells characteristics according to the ISCT and their conditioned medium (CM) inhibited LPS-stimulated murine bone marrow neutrophils neutrophil extracellular traps (NETs) release

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Summary

Introduction

It has been described that TSG-6 secreted from bone marrow MSC possesses anti-inflammatory and immunomodulatory mechanisms in a murine traumatic brain injury[20] It has been demonstrated the direct effect of secreted TSG-6 from human bone marrow mesenchymal stem cells by inhibiting the immune response through p38 and MEK mitogen-activated protein kinase pathway[21]. It has been shown that hAM mesoderm is able to suppress the adaptive and innate immune responses[22,23,24]. In this context, there are cells that can be obtained from the hAM mesoderm; these are the human amniotic mesenchymal stromal cells (hAMSC). The aim of this study was to describe the role of TSG-6 produced by hAMSC on NETs release

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