Manufacturing Mesenchymal Stromal Cells for the Treatment of Graft-versus-Host Disease: A Survey among Centers Affiliated with the European Society for Blood and Marrow Transplantation.

The immunosuppressive properties of mesenchymal stromal cells (MSC) have been successfully tested to control clinical severe graft-versus host disease and improve survival. However, clinical studies have not yet provided conclusive evidence of their efficacy largely because of lack of patients' stratification criteria. The heterogeneity of MSC preparations is also a major contributing factor, as manufacturing of therapeutic MSC is performed according to different protocols among different centers.

Osteocalcin positive mononuclear cells are associated with the severity of aortic calcification.

Objective: To assess the association of circulating bone marrow-derived osteo-progenitors with vascular calcification in mouse models and patients with peripheral artery disease.

Methods: We estimated the percentage of circulating mononuclear cells expressing osteocalcin in 2 mouse models of aortic calcification developed in osteoprotegerin-deficient mice (OPG(-/-)) using flow cytometry. Aortic calcification was assessed in mice principally by a bioassay of harvested aortas.

Osteoprotegerin, vascular calcification and atherosclerosis.

The association of bone pathologies with atherosclerosis has stimulated the search for common mediators linking the skeletal and the vascular system. Since its initial discovery as a key regulator in bone metabolism, osteoprotegerin (OPG) has become the subject of intense interest for its role in vascular disease and calcification. Studies in vitro and in animal models suggest that OPG inhibits vascular calcification.

Role of homocysteine in aortic calcification and osteogenic cell differentiation.

Background: The role of homocysteine in atherosclerosis is unclear. We examined the relationship between plasma homocysteine and infrarenal aortic calcification, the presence of homocysteine in human atheroma and the influence of homocysteine on osteogenic differentiation in vitro.

Methods And Results: In 194 patients with symptomatic peripheral artery disease or abdominal aortic aneurysm, fasting plasma total homocysteine was independently associated with the severity of infrarenal aortic calcification measured by Computer Tomography Angiography (odds ratio 1.

Bone marrow-derived cells and arterial disease.

This article reviews the association between bone and artery disease, with particular relevance to progenitor cells. The review was based on insight gained by analysis of previous publications and on-going work by the authors. A large number of studies have demonstrated a correlation between bone pathology, particularly osteoporosis, and atherosclerosis.

Osteoprotegerin upregulates endothelial cell adhesion molecule response to tumor necrosis factor-alpha associated with induction of angiopoietin-2.

Objective: Osteoprotegerin (OPG) and osteopontin (OPN) have been identified within unstable atherosclerosis and circulating concentrates have been linked to cardiovascular events. We studied the influence of OPG and OPN on endothelial adhesion molecule expression and monocyte binding.

Methods: Resting or tumor necrosis factor (TNF-alpha) activated human endothelial cells were incubated with OPG (0, 0.

Iron-induced oxidative stress in haemodialysis patients: a pilot study on the impact of diabetes.

Background: Administration of intravenous iron preparations in haemodialysis patients may lead to the appearance of non-transferrin bound iron which can catalyse oxidative damage. We investigated this hypothesis by monitoring the oxidative stress of haemodialysis patients and the impact of iron and diabetes mellitus herein.

Materials And Methods: Baseline values of serum iron and related proteins, transferrin glycation, non-transferrin bound iron, antioxidant capacity and lipid peroxidation (malondialdehyde) of 11 haemodialysis patients (six non-diabetic and five type 2 diabetes) were compared to those of non-haemodialysis control subjects (non-diabetic and type 2 diabetes).

Iron-binding antioxidant capacity is impaired in diabetes mellitus.

Increased lipid peroxidation contributes to diabetic complications and redox-active iron is known to play an important role in catalyzing peroxidation reactions. We aimed to investigate if diabetes affects the capacity of plasma to protect against iron-driven lipid peroxidation and to identify underlying factors. Glycemic control, serum iron, proteins involved in iron homeostasis, plasma iron-binding antioxidant capacity in a liposomal model, and non-transferrin-bound iron were measured in 40 type 1 and 67 type 2 diabetic patients compared to 100 nondiabetic healthy control subjects.

A novel method to quantify in vivo transferrin glycation: applications in diabetes mellitus.

Background: In vitro glycation of transferrin leads to increased oxidative stress by impairing iron-binding antioxidant capacity. The aim of this study is to develop a method to evaluate in vivo transferrin glycation in diabetes.

Methods: We adapted the nitroblue tetrazolium assay to measure in micro-well plates the fructosamine content of transferrin isolated from serum by immunocomplexation.

Impact of diabetes mellitus on the relationships between iron-, inflammatory- and oxidative stress status.

Background: Diabetes is an inflammatory condition associated with iron abnormalities and increased oxidative damage. We aimed to investigate how diabetes affects the interrelationships between these pathogenic mechanisms.

Methods: Glycaemic control, serum iron, proteins involved in iron homeostasis, global antioxidant capacity and levels of antioxidants and peroxidation products were measured in 39 type 1 and 67 type 2 diabetic patients and 100 control subjects.

Time course of oxidative stress status in the postprandial and postabsorptive states in type 1 diabetes mellitus: relationship to glucose and lipid changes.

Objective: The aim of this study was to compare oxidative stress status (OSS) with blood glucose and lipid changes during the fasting, postprandial and postabsorptive phases in type 1 diabetes mellitus.

Methods: Twenty-three patients on intensive insulin treatment received a standard fat-rich breakfast and lunch. OSS was monitored at fasting (F), just after the post-breakfast glycemia peak (BP) (identified by continuous subcutaneous glucose monitoring), 3.

Cell-mediated LDL oxidation: the impact of transition metals and transferrin.

Activated monocytes release oxygen radicals by respiratory burst and oxidative damage can be accelerated by transition metals. We investigated the cell-mediated and metal-catalysed in vitro oxidation of low-density lipoproteins (LDL), as well as the impact of the metal-binding protein transferrin (Tf). LDL oxidation was measured by monitoring the increase in fluorescence (350/440 nm excitation/emission).

Evolution of serum alpha-tocopherol in the postprandial and postabsorptive phases in type 1 diabetes mellitus.

Blood glucose, lipids, alpha-tocopherol, and malondialdehyde were monitored in type 1 diabetes mellitus patients for 8 hours after a standard fat-rich breakfast and lunch. Although glucose and triglycerides increased, alpha-tocopherol decreased and malondialdehyde increased in the postprandial phase. In the postabsorptive phase values returned to fasting levels.

Effects of in vitro glycation on Fe3+ binding and Fe3+ isoforms of transferrin.

Background: In diabetes, protein function is altered by glycation, but the impact on the Fe3+ binding and antioxidant functions of transferrin (Tf) is largely unknown. The aim of the present study was to investigate the effects of glycation on the distribution of Fe3+ on the two Fe3+ -binding sites of Tf.

Methods: In vitro glycation of Tf was accomplished by preincubation with glucose for 14 days.

Transferrin modifications and lipid peroxidation: implications in diabetes mellitus.

Free iron is capable of stimulating the production of free radicals which cause oxidative damage such as lipid peroxidation. One of the most important mechanisms of antioxidant defense is thus the sequestration of iron in a redox-inactive form by transferrin. In diabetes mellitus, increased oxidative stress and lipid peroxidation contribute to chronic complications but it is not known if this is related to abnormalities in transferrin function.