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Tissue engineering of large bone defects is approached through implantation of autologous osteogenic cells, generally referred to as multipotent stromal cells or mesenchymal stem cells (MSCs). Animal-derived MSCs successfully bridge large bone defects, but models for ectopic bone formation as well as recent clinical trials demonstrate that bone formation by(More)
In mammalian cells transcription factors of the AP-1 family are activated by either stress signals such as UV radiation, or mitogenic signals such as growth factors. Here we show that a similar situation exists in the yeast Saccharomyces cerevisiae. The AP-1 transcriptional activator Gcn4, known to be activated by stress signals such as UV radiation and(More)
The use of multipotent human mesenchymal stem cells (hMSCs) for tissue engineering has been a subject of extensive research. The donor variation in growth, differentiation and in vivo bone forming ability of hMSCs is a bottleneck for standardization of therapeutic protocols. In this study, we isolated and characterized hMSCs from 19 independent donors, aged(More)
Antibodies against nucleosomes are a serological hallmark of systemic lupus erythematosus (SLE). Apoptotic cells are the unique source of nucleosomes, which are formed through cleavage of chromatin by nucleases. These nucleosomes and other autoantigens targeted in SLE are expressed in apoptotic blebs or at the surface of apoptotic cells. Therefore, it is(More)
The cardinal feature of systemic lupus erythematosus is the formation of anti-nuclear antibodies. In recent years, it has become clear that the nucleosome is a major autoantigen that drives this T cell-dependent autoimmune response, as exemplified by the presence of nucleosome-specific T helper cells and the high prevalence of nucleosome-specific(More)
OBJECTIVE To evaluate the effect of disease progression and lipopolysaccharide (LPS) administration on the presence of nucleosomes, antinucleosome reactivity, and nucleosome-Ig complexes in the circulation of MRL and control mice. METHODS Plasma samples from lupus-prone (MRL/lpr and MRL/+) and control (CBA, Swiss, and BALB/c) mice were tested in(More)
Our approach to bone tissue engineering is the in vitro expansion and osteogenic differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) and their subsequent implantation on porous ceramic materials. Current osteogenic differentiation protocols use dexamethasone to initiate the osteogenic process, thus ignoring the multiple signaling(More)
Antibodies against nucleosomes are a hallmark of systemic lupus erythematosus (SLE). Nucleosomes are uniquely formed during apoptosis, through cleavage of chromatin by nucleases. Increased exposure of nucleosomes to the immune system could play a role in the induction of the autoimmune repertoire in SLE. To determine whether there exists a constitutive(More)
Research into the mechanisms by which apoptotic cells are phagocytosed has grown considerably over recent years, together with a growing appreciation of the importance of clearance of redundant cells for tissue homeostasis. However, studies addressing the efficacy of phagocytosis have been rare. The few studies reported to date were either attempts to(More)
Electrospinning (ESP) has lately shown a great potential as a novel scaffold fabrication technique for tissue engineering. Scaffolds are produced by spinning a polymeric solution in fibers through a spinneret connected to a high-voltage electric field. The fibers are then collected on a support, where the scaffold is created. Scaffolds can be of different(More)