Abstract

Menstrual blood-derived stromal cells (MenSCs) are emerging as a strong candidate for cell-based therapies due to their immunomodulatory properties. However, their direct impact on innate immune populations remains elusive. Since macrophages play a key role in the onset and development of inflammation, understanding MenSCs implication in the functional properties of these cells is required to refine their clinical effects during the treatment of inflammatory disorders. In this study, we assessed the effects that MenSCs had on the recruitment of macrophages and other innate immune cells in two mouse models of acute inflammation, a thioglycollate (TGC)-elicited peritonitis model and a monobacterial sepsis model. We found that, in the TGC model, MenSCs injection reduced the percentage of macrophages recruited to the peritoneum and promoted the generation of peritoneal immune cell aggregates. In the sepsis model, MenSCs exacerbated infection by diminishing the recruitment of macrophages and neutrophils to the site of infection and inducing defective bacterial clearance. Additional in vitro studies confirmed that co-culture with MenSCs impaired macrophage bactericidal properties, affecting bacterial killing and the production of reactive oxygen intermediates. Our findings suggest that MenSCs modulate the macrophage population and that this modulation must be taken into consideration when it comes to future clinical applications.

Highlights

  • Menstrual blood-derived stromal cells (MenSCs) are emerging as a strong candidate for cell-based therapies due to their immunomodulatory properties

  • The purpose of this study was to evaluate the immunomodulatory effects that MenSCs have on macrophages during the early stages of acute inflammation using two mouse models: a thioglycollate (TGC)-elicited peritonitis model and a monobacterial sepsis model induced by Salmonella Typhimurium strains

  • Injection of MenSCs alters the number and percentage of innate immune populations recruited to the peritoneum in a TGC‐elicited peritonitis mouse model

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Summary

Introduction

Menstrual blood-derived stromal cells (MenSCs) are emerging as a strong candidate for cell-based therapies due to their immunomodulatory properties. MenSCs share characteristics with other MSCs such as being plastic-adherent cells, expressing typical mesenchymal stromal cell surface markers, being capable of differentiating into mesodermal cell lineages in vitro and displaying a low immunogenic ­profile[1,2], which makes them a good candidate for clinical use in cell-based therapies. Since their first characterisation by Meng et al.[1] in 2007, MenSCs have aroused great interest as an alternative source of MSCs other than bone m­ arrow[3], adipose t­issue[4] or birth-associated tissues—such as umbilical ­cord[5], cord ­blood6, ­decidua[7] and ­placenta8—due to their ease of obtainment. Since the tissue source is a factor that might contribute to the particular functional properties and effects exerted by MSCs, one must be cautious when extrapolating the immunomodulatory properties of MSCs from different

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