title: Transplantation of human fetal blood stem cells in the osteogenesis imperfecta mouse leads to improvement in multiscale tissue properties.
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.
authors.affiliation: Department of Bioengineering, Imperial College, London, UK.
authors.forename: Maximilien
authors.initials: M
authors.lastname: Vanleene
authors.forename: Zahraa
authors.initials: Z
authors.lastname: Saldanha
authors.forename: Kristy L
authors.initials: KL
authors.lastname: Cloyd
authors.forename: Gavin
authors.initials: G
authors.lastname: Jell
authors.forename: George
authors.initials: G
authors.lastname: Bou-Gharios
authors.forename: J H Duncan
authors.initials: JH
authors.lastname: Bassett
authors.forename: Graham R
authors.initials: GR
authors.lastname: Williams
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Fisk
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Oyen
authors.forename: Molly M
authors.initials: MM
authors.lastname: Stevens
authors.forename: Pascale V
authors.initials: PV
authors.lastname: Guillot
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Shefelbine
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D015153:Blotting, Western; D002454:Cell Differentiation; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D005264:Femoral Fractures / Q000517:prevention & control; D005269:Femur / Q000378:metabolism / Q000503:physiopathology; D053686:Fetal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D050723:Fractures, Bone / Q000517:prevention & control*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010013:Osteogenesis Imperfecta / Q000235:genetics / Q000601:surgery*; D011247:Pregnancy; D025341:Principal Component Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013059:Spectrum Analysis, Raman; D014183:Transplantation, Heterologous
chemical_list: D024042:Collagen Type I; D015675:Osteocalcin; D003094:Collagen