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.
Subject(s)
Human Umbilical Vein Endothelial Cells/drug effects , Hydrogen Peroxide/pharmacology , Mesenchymal Stem Cells/drug effects , Monocytes/metabolism , Oxidative Stress/drug effects , Adult , Antigens, CD/genetics , Antigens, CD/metabolism , Biomarkers/metabolism , Cell Adhesion/drug effects , Cell Adhesion Molecules/genetics , Cell Adhesion Molecules/metabolism , Cell Proliferation/drug effects , Coculture Techniques , Culture Media, Conditioned/pharmacology , Decidua/cytology , Decidua/metabolism , Female , Gene Expression , Glutathione Reductase/genetics , Glutathione Reductase/metabolism , Human Umbilical Vein Endothelial Cells/cytology , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Monocytes/cytology , Pregnancy , Thioredoxin-Disulfide Reductase/genetics , Thioredoxin-Disulfide Reductase/metabolism , Umbilical Cord/cytology , Umbilical Cord/metabolismABSTRACT
BACKGROUND: Mesenchymal stem/stromal cells derived from chorionic villi of human term placentae (pMSCs) protect human endothelial cells from injury induced by hydrogen peroxide (H2O2). In diabetes, elevated levels of glucose (hyperglycaemia) induce H2O2 production, which causes the endothelial dysfunction that underlies the enhanced immune responses and adverse complications associated with diabetes, which leads to thrombosis and atherosclerosis. In this study, we examined the ability of pMSCs to protect endothelial cell functions from the negative impact of high level of glucose. METHODS: pMSCs isolated from the chorionic villi of human term placentae were cultured with endothelial cells isolated from human umbilical cord veins in the presence of glucose. Endothelial cell functions were then determined. The effect of pMSCs on gene expression in glucose-treated endothelial cells was also determined. RESULTS: pMSCs reversed the effect of glucose on key endothelial cell functions including proliferation, migration, angiogenesis, and permeability. In addition, pMSCs altered the expression of many genes that mediate important endothelial cell functions including survival, apoptosis, adhesion, permeability, and angiogenesis. CONCLUSIONS: This is the first comprehensive study to provide evidence that pMSCs protect endothelial cells from glucose-induced damage. Therefore, pMSCs have potential therapeutic value as a stem cell-based therapy to repair glucose-induced vascular injury and prevent the adverse complications associated with diabetes and cardiovascular disease. However, further studies are necessary to reveal more detailed aspects of the mechanism of action of pMSCs on glucose-induced endothelial damage in vitro and in vivo.
Subject(s)
Culture Media, Conditioned/pharmacology , Gene Expression Regulation/drug effects , Glucose/pharmacology , Human Umbilical Vein Endothelial Cells/drug effects , Mesenchymal Stem Cells/metabolism , Apoptosis/drug effects , Cell Membrane Permeability/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Chemokines/genetics , Chemokines/metabolism , Chorionic Villi/metabolism , Coculture Techniques , Collagen/chemistry , Collagen/genetics , Collagen/metabolism , Drug Combinations , Endothelins/genetics , Endothelins/metabolism , Female , Glucose/antagonists & inhibitors , Human Umbilical Vein Endothelial Cells/cytology , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Interleukins/genetics , Interleukins/metabolism , Laminin/chemistry , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Mesenchymal Stem Cells/cytology , Pregnancy , Proteoglycans/chemistry , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , Signal Transduction , THP-1 Cells , Umbilical Cord/cytology , Umbilical Cord/metabolismABSTRACT
Mesenchymal stem/stromal cells derived from chorionic villi of human term placentae (pMSCs) produce a unique combination of molecules, which modulate important cellular functions of their target cells while concurrently suppressing their immune responses. These properties make MSCs advantageous candidates for cell-based therapy. Our first aim was to examine the effect of high levels of oxidative stress on pMSC functions. pMSCs were exposed to hydrogen peroxide (H2O2) and their ability to proliferate and adhere to an endothelial cell monolayer was determined. Oxidatively stressed pMSCs maintained their proliferation and adhesion potentials. The second aim was to measure the ability of pMSCs to prevent oxidative stress-related damage to endothelial cells. Endothelial cells were exposed to H2O2, then co-cultured with pMSCs, and the effect on endothelial cell adhesion, proliferation and migration was determined. pMSCs were able to reverse the damaging effects of oxidative stress on the proliferation and migration but not on the adhesion of endothelial cells. These data indicate that pMSCs are not only inherently resistant to oxidative stress, but also protect endothelial cell functions from oxidative stress-associated damage. Therefore, pMSCs could be used as a therapeutic tool in inflammatory diseases by reducing the effects of oxidative stress on endothelial cells.
Subject(s)
Cell- and Tissue-Based Therapy , Endothelial Cells/physiology , Mesenchymal Stem Cells/physiology , Oxidative Stress , Placenta/cytology , Cell Adhesion , Cell Movement , Female , Human Umbilical Vein Endothelial Cells , Humans , Hydrogen Peroxide , PregnancyABSTRACT
Mesenchymal stem/stromal cells (MSCs) are isolated from various fetal and adult tissues such as bone marrow, adipose tissue, cord blood and placenta. Placental MSCs (pMSCs), the main focus of this review, are relatively new MSC types that are not as intensively studied compared with bone marrow-derived MSCs (BMMSCs). MSCs modulate the immune functions of important immune cells involved in alloantigen recognition and elimination, including antigen presenting cells (APCs), T cells, B cells and natural killer (NK) cells. Clinical trials, both completed and underway, employ MSCs to treat various human immunological diseases, such as multiple sclerosis (MS) and type 1 diabetes. However, the mechanisms that mediate the immunosuppressive effects of pMSCs are still largely unknown, and the safety of pMSC use in clinical settings needs further confirmation. Here, we review the current knowledge of the immunosuppressive properties of placental MSCs.
