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Dendritic cell (DC)-mediated cross-presentation of exogenous antigens acquired in the periphery is critical for the initiation of CD8(+) T cell responses. Several DC subsets are described in human tissues but migratory cross-presenting DCs have not been isolated, despite their potential importance in immunity to pathogens, vaccines, and tumors and tolerance(More)
Correction of perinatally lethal neurogenetic diseases requires efficient transduction of several cell types within the relatively inaccessible CNS. Intravenous AAV9 delivery in mouse has achieved development stage-specific transduction of neuronal cell types, with superior neuron-targeting efficiency demonstrated in prenatal compared with postnatal(More)
Osteoporosis and other diseases of bone loss are a major public health problem. Here it is shown that the statins, drugs widely used for lowering serum cholesterol, also enhance new bone formation in vitro and in rodents. This effect was associated with increased expression of the bone morphogenetic protein-2 (BMP-2) gene in bone cells. Lovastatin and(More)
Fetal cells enter maternal blood during pregnancy and persist in women with autoimmune disease. The frequency of subsequent fetomaternal microchimerism in healthy women and its cell type is unknown. To test the hypothesis that fetal mesenchymal stem cells persist in maternal organs, we studied female bone marrow and ribs. Male cells were identified by XY(More)
The inherited skeletal dysplasia osteogenesis imperfecta (OI) results in multiple fractures and is currently treated empirically. We transplanted human first-trimester fetal blood mesenchymal stem cells (MSCs) into homozygous oim mice in utero. This resulted in a two-thirds reduction in long bone fractures (P < .01), with fewer fractures per mouse (median(More)
Mesenchymal stem cells (MSC) from fetal-placental tissues have translational advantages over their adult counterparts, and have variably been reported to express pluripotency markers. OCT- 4 expression in fetal-placental MSC has been documented in some studies, paradoxically without tumourogenicity in vivo. It is possible that OCT- 4 expression is(More)
Chagas' disease, caused by the protozoan parasite, Trypanosoma cruzi, is associated with gastrointestinal abnormalities. Since nitric oxide (NO) has been shown to be a factor influencing intestinal function we evaluated the distributions and activities of the NO synthase (NOS) isoforms, in the gut of mice infected with T. cruzi. Ca2+-dependent (NOS1/NOS3)(More)
Fetal mesenchymal stem/stromal cells (MSC) represent a developmentally-advantageous cell type with translational potential. To enhance adult MSC migration, studies have focussed on the role of the chemokine receptor CXCR4 and its ligand SDF-1 (CXCL12), but more recent work implicates an intricate system of CXCR4 receptor dimerization, intracellular(More)
BACKGROUND Intrauterine stem cell transplantation is a promising approach for early onset genetic diseases. However, its utility is limited by the development of the fetal immune system after 14 weeks gestation. An ex vivo gene therapy approach targeting autologous first trimester stem cells to replace the missing or defective gene product should overcome(More)