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BACKGROUND Bone marrow-derived mesenchymal stem cells (MSC) improve myocardial recovery after ischemia/reperfusion (I/R) injury. These effects are mediated in part by the paracrine secretion of angiogenic and tissue growth-promoting factors. Toll-like receptor 4 (TLR4) is expressed by MSC and induces apoptosis and inhibits proliferation in neuronal(More)
Optimizing the function and proliferative capacity of stem cells is essential to maximize their therapeutic benefits. High glucose concentrations are known to have detrimental effects on many cell types. We hypothesized that human mesenchymal stem cells (hMSCs) cultured in high glucose-containing media would exhibit diminished proliferation and attenuated(More)
Females have a lower incidence of heart failure and improved survival after myocardial ischemia-reperfusion (I/R) compared with males. Although estrogen-suppressed cardiomyocyte apoptosis may be mediated through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway, it is unclear whether this action is mediated via estrogen receptor beta(More)
BACKGROUND Cardiac surgery induces the release of inflammatory mediators that can prolong cardiac dysfunction after operative intervention. Interleukin-10 (IL-10), a potent inhibitor of myocardial inflammation, is a known factor in myocardial protection after ischemia/reperfusion (I/R) injury. We hypothesized that IL-10 activity during initial reperfusion(More)
BACKGROUND Transforming growth factor-α (TGF-α) has been shown to augment mesenchymal stem cell-mediated cardioprotection during acute ischemia and reperfusion in isolated heart models. To determine whether this pretreatment strategy would be effective in vivo, we hypothesized that the intramyocardial injection of mesenchymal stem cells pretreated with(More)
Mesenchymal stem cells (MSCs) are a promising therapy for acute organ ischemia in part due to their paracrine production of growth factors. However, transplanted cells encounter an inflammatory environment that mitigates their function and survival, and treating the cells with exogenous agents during ex vivo expansion before transplantation is one strategy(More)
BACKGROUND Estrogen may protect against the development of cardiovascular disease. Recently, a receptor known as GPR30 that seems to mediate estrogen's nongenomic effects has been identified. We hypothesized that the activation of GPR30 protects cardiac function and decreases myocardial inflammation after global ischemia/reperfusion (I/R). METHODS Hearts(More)
BACKGROUND Mesenchymal stem cells (MSCs) improve postischemic myocardial function in part through their secretion of growth factors such as vascular endothelial growth factor (VEGF). Pretreating MSCs with various cytokines or small molecules can improve VEGF secretion and MSC-mediated cardioprotection. However, whether 1 cytokine can potentiate the effect(More)
BACKGROUND Endotoxemia is associated with depressed cardiac function during sepsis. Mesenchymal stem cells (MSCs) possess an ability to modulate the inflammatory response during sepsis, but it is unknown whether MSCs possess the ability to reduce endotoxemia-induced myocardial injury and dysfunction. METHODS Endotoxemia was induced in rats via injection(More)
Human bone marrow mesenchymal stem cells (MSCs) are a potent source of growth factors, which are partly responsible for their beneficial paracrine effects. We reported previously that transforming growth factor-alpha (TGF-alpha), a putative mediator of wound healing and the injury response, increases the release of vascular endothelial growth factor (VEGF),(More)