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Transplantation of human fetal blood stem cells in the osteogenesis imperfecta mouse leads to improvement in multiscale tissue properties

Vanleene, M; Saldanha, Z; Cloyd, KL; Jell, G; Bou-Gharios, G; Bassett, JHD; ... Shefelbine, SJ; + view all (2011) Transplantation of human fetal blood stem cells in the osteogenesis imperfecta mouse leads to improvement in multiscale tissue properties. BLOOD , 117 (3) 1053 - 1060. 10.1182/blood-2010-05-287565.

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Abstract

Osteogenesis imperfecta (OI or brittle bone disease) is a disorder of connective tissues caused by mutations in the collagen genes. We previously showed that intrauterine transplantation of human blood fetal stem/stromal cells in OI mice (oim) resulted in a significant reduction of bone fracture. This work examines the cellular mechanisms and mechanical bone modifications underlying these therapeutic effects, particularly examining the direct effects of donor collagen expression on bone material properties. In this study, we found an 84% reduction in femoral fractures in transplanted oim mice. Fetal blood stem/stromal cells engrafted in bones, differentiated into mature osteoblasts, expressed osteocalcin, and produced COL1a2 protein, which is absent in oim mice. The presence of normal collagen decreased hydroxyproline content in bones, altered the apatite crystal structure, increased the bone matrix stiffness, and reduced bone brittleness. In conclusion, expression of normal collagen from mature osteoblast of donor origin significantly decreased bone brittleness by improving the mechanical integrity of the bone at the molecular, tissue, and whole bone levels. (Blood. 2011; 117(3): 1053-1060)

Type:Article
Title:Transplantation of human fetal blood stem cells in the osteogenesis imperfecta mouse leads to improvement in multiscale tissue properties
DOI:10.1182/blood-2010-05-287565
Keywords:IN-UTERO TRANSPLANTATION, BONE-MARROW, MECHANICAL-PROPERTIES, ALENDRONATE TREATMENT, MESENCHYMAL CELLS, SKELETAL-MUSCLE, CORTICAL BONE, MURINE MODEL, NANOINDENTATION, INDENTATION
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of) > Research Department of General Surgery
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Women's Health > Maternal and Fetal Medicine

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