Abstract
The immunomodulatory properties of human endometrial mesenchymal stem cells (eMSC) have not been well characterised. Initial studies showed that eMSC modulated the chronic inflammatory response to a non-degradable polyamide/gelatin mesh in a xenogeneic rat skin wound repair model, but the mechanism remains unclear. In this study, we investigated the immunomodulatory effect of eMSC on the macrophage response to polyamide/gelatin composite mesh in an abdominal subcutaneous wound repair model in C57BL6 immunocompetent and NSG (NOD-Scid-IL2Rgammanull) immunocompromised mice to determine whether responses differed in the absence of an adaptive immune system and NK cells. mCherry lentivirus-labelled eMSC persisted longer in NSG mice, inducing longer term paracrine effects. Inclusion of eMSC in the mesh reduced inflammatory cytokine (Il-1β, Tnfα) secretion, and in C57BL6 mice reduced CCR7+ M1 macrophages surrounding the mesh on day 3 and increased M2 macrophage marker mRNA (Arg1, Mrc1, Il10) expression at days 3 and 7. In NSG mice, these effects were delayed and only observed at days 7 and 30 in comparison with controls implanted with mesh alone. These results show that the differences in the immune status in the two animals directly affect the survival of xenogeneic eMSC which leads to differences in the short-term and long-term macrophage responses to implanted meshes.
Highlights
Complications in approximately 10% of women[11] including mesh erosion, mesh contracture, infection and pain[12]
In order to track the cells in vivo, endometrial MSC (eMSC) purified by SUSD2 magnetic bead sorting were transduced with mCherry lentiviral vector and the SUSD2+mCherry+ cells were sorted and cultured in DMEM medium containing 10% FBS
It is likely that eMSC exerted these immunomodulatory effects via a paracrine mechanism in both mouse models
Summary
Complications in approximately 10% of women[11] including mesh erosion, mesh contracture, infection and pain[12]. Clonogenic eMSC can be purified using co-expression of CD140b and CD146 with a cell sorter or by a single marker, SUSD2 (recognised by the W5C5 antibody) using magnetic bead sorting[19,20] These perivascular eMSC fulfil the International Society for Cellular Therapies minimal MSC criteria, are highly proliferative, self-renew in vitro and reconstitute stromal tissue in vivo[19,21]. We have shown the efficacy of using eMSC in PA + G mesh[23] to deliver eMSC in a small animal model of wound repair[24] In this xenogeneic model, human eMSC exerted a paracrine effect promoting wound healing, angiogenesis and neo tissue formation. In an endotoxin-induced lung injury model, intrapulmonary delivery of mouse bmMSC decreased the production of Tnfα and Chemokine Ligand 2 (CXCL2) and increased alveolar macrophage secretion of Il1032
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