Human decidua basalis mesenchymal stem/stromal cells protect endothelial cell functions from oxidative stress induced by hydrogen peroxide and monocytes

Abstract Background Human decidua basalis mesenchymal stem/multipotent stromal cells (DBMSCs) inhibit endothelial cell activation by inflammation induced by monocytes. This property makes them a promising candidate for cell-based therapy to treat inflammatory diseases, such as atherosclerosis. This study was performed to examine the ability of DBMSCs to protect endothelial cell functions from the damaging effects resulting from exposure to oxidatively stress environment induced by H2O2 and monocytes. Methods DBMSCs were co-cultured with endothelial cells isolated from human umbilical cord veins in the presence of H2O2 and monocytes, and various functions of endothelial cell were then determined. The effect of DBMSCs on monocyte adhesion to endothelial cells in the presence of H2O2 was also examined. In addition, the effect of DBMSCs on HUVEC gene expression under the influence of H2O2 was also determined. Results DBMSCs reversed the effect of H2O2 on endothelial cell functions. In addition, DBMSCs reduced monocyte adhesion to endothelial cells and also reduced the stimulatory effect of monocytes on endothelial cell proliferation in the presence of H2O2. Moreover, DBMSCs modified the expression of many genes mediating important endothelial cell functions. Finally, DBMSCs increased the activities of glutathione and thioredoxin reductases in H2O2-treated endothelial cells. Conclusions We conclude that DBMSCs have potential for therapeutic application in inflammatory diseases, such as atherosclerosis by protecting endothelial cells from oxidative stress damage. However, more studies are needed to elucidate this further

Preconditioning by Hydrogen Peroxide Enhances Multiple Properties of Human Decidua Basalis Mesenchymal Stem/Multipotent Stromal Cells

Stem cell-based therapies rely on stem cell ability to repair in an oxidative stress environment. Preconditioning of mesenchymal stem cells (MSCs) to a stress environment has beneficial effects on their ability to repair injured tissues. We previously reported that MSCs from the decidua basalis (DBMSCs) of human placenta have many important cellular functions that make them potentially useful for cell-based therapies. Here, we studied the effect of DBMSC preconditioning to a stress environment. DBMSCs were exposed to various concentrations of hydrogen peroxide (H2O2), and their functions were then assessed. DBMSC expression of immune molecules after preconditioning was also determined. DBMSC preconditioning with H2O2 enhanced their proliferation, colonogenicity, adhesion, and migration. In addition, DBMSCs regardless of H2O2 treatment displayed antiangiogenic activity. H2O2 preconditioning also increased DBMSC expression of genes that promote cellular functions and decreased the expression of genes, which have opposite effect on their functions. Preconditioning also reduced DBMSC expression of IL-1β, but had no effects on the expression of other immune molecules that promote proliferation, adhesion, and migration. These data show that DBMSCs resist a toxic environment, which adds to their potential as a candidate stem cell type for treating various diseases in hostile environments

Characterization of the interaction between human decidua parietalis mesenchymal stem/stromal cells and natural killer cells

Abstract Background Human decidua parietalis mesenchymal stem/multipotent stromal cells (DPMSCs) have unique phenotypic and functional properties that make them promising candidates for cell-based therapy. Here, we investigated DPMSC interaction with natural killer (NK) cells, and the effects of this interaction on NK cell phenotypic characteristics and functional activities. Methods DPMSCs isolated from the decidua parietalis of human fetal membranes were cultured with interleukin (IL)-2-activated and IL-2-unactivated NK cells isolated from healthy human peripheral blood. NK cell proliferation and cytolytic activities were then examined using functional assays. NK cell expression of receptors mediating the cytolytic activity against DPMSCs, and the mechanism underlying this effect on DPMSCs, were also examined using flow cytometry and light microscopy, respectively. Results DPMSCs stimulated IL-2-induced proliferation of resting NK cells and the proliferation of activated NK cells. Moreover, IL-2-activated NK cells, but not freshly isolated NK cells, efficiently lysed DPMSCs. The induction of this NK cell cytolytic activity against DPMSCs was mediated by the activating NK cell receptors NKG2D, CD69, NKp30, and NKp44. However, DPMSCs showed a direct induction of NK cell cytolytic activity through CD69. We also found that DPMSCs expressed the ligands for these activating NK cell receptors including Nectin-2, ULBP-2, MICA, and MICB. Although DPMSCs expressed HLA class I molecules, they were susceptible to lysis by NK cells, suggesting that HLA class I antigens do not play a significant role in NK cell cytolytic action. In addition, DPMSCs did not inhibit NK cell cytolytic activity against cancer cells. Importantly, DPMSCs significantly increased NK expression of inflammatory molecules with anticancer activities. Conclusions We conclude that DPMSCs have potential for therapeutic application in cancer therapy, but not in transplantation or immunological diseases

Preconditioning human natural killer cells with chorionic villous mesenchymal stem cells stimulates their expression of inflammatory and anti-tumor molecules

Abstract Background Mesenchymal stem cells derived from the chorionic villi of human placentae (pMSCs) produce a unique array of mediators that regulate the essential cellular functions of their target cells. These properties make pMSCs attractive candidates for cell-based therapy. Here, we examined the effects of culturing human natural killer (NK) cells with pMSCs on NK cell functions. Methods pMSCs were cultured with IL-2-activated and non-activated NK cells. NK cell proliferation and cytolytic activities were monitored. NK cell expression of receptors mediating their cytolytic activity against pMSCs, and the mechanisms underlying this effect on pMSCs, were also investigated. Results Our findings show that IL-2-activated NK cells, but not freshly isolated NK cells, efficiently lyse pMSCs and that this response might involve the activating NK cell receptor CD69. Interestingly, although pMSCs expressed HLA class I molecules, they were nevertheless lysed by NK cells, suggesting that HLA class I antigens do not play a significant role in protecting pMSCs from NK cell cytolytic activity. Co-culturing NK cells with pMSCs also inhibited NK cell expression of receptors, including CD69, NKpG2D, CD94, and NKp30, although these co-cultured NK cells were not inhibited in lysing cancer cells in vitro. Importantly, co-cultured NK cells significantly increased their production of molecules with anti-tumor effects. Conclusions These findings suggest that pMSCs might have potential applications in cancer therapy

IFPA Meeting 2013 Workshop Report III: maternal placental immunological interactions, novel determinants of trophoblast cell fate, dual ex vivo perfusion of the human placenta.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At IFPA meeting 2013 there were twelve themed workshops, three of which are summarized in this report. These workshops related to various aspects of placental biology but collectively covered areas of placental function, cell turnover and immunology: 1) immunology; 2) novel determinants of placental cell fate; 3) dual perfusion of human placental tissue