title: Counteracting bone fragility with human amniotic mesenchymal stem cells.
abstract: The impaired maturation of bone-forming osteoblasts results in reduced bone formation and subsequent bone weakening, which leads to a number of conditions such as osteogenesis imperfecta (OI). Transplantation of human fetal mesenchymal stem cells has been proposed as skeletal anabolic therapy to enhance bone formation, but the mechanisms underlying the contribution of the donor cells to bone health are poorly understood and require further elucidation. Here, we show that intraperitoneal injection of human amniotic mesenchymal stem cells (AFSCs) into a mouse model of OI (oim mice) reduced fracture susceptibility, increased bone strength, improved bone quality and micro-architecture, normalised bone remodelling and reduced TNFα and TGFβ sigalling. Donor cells engrafted into bones and differentiated into osteoblasts but importantly, also promoted endogenous osteogenesis and the maturation of resident osteoblasts. Together, these findings identify AFSC transplantation as a countermeasure to bone fragility. These data have wider implications for bone health and fracture reduction.
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Ranzoni
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Corcelli
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Kwan-Leong
authors.initials: KL
authors.lastname: Hau
authors.affiliation: Lancaster Medical School, Lancaster University, Lancaster, UK.
authors.forename: Jemma G
authors.initials: JG
authors.lastname: Kerns
authors.affiliation: ONCOLille, Regional University Hospital of Lille, Lille, France.
authors.forename: Maximilien
authors.initials: M
authors.lastname: Vanleene
authors.affiliation: Department of Mechanical and Industrial Engineering, Northeastern University, Boston MA, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Shefelbine
authors.affiliation: Institute of Reproduction and Developmental Biology, Imperial College London, London, UK.
authors.forename: Gemma N
authors.initials: GN
authors.lastname: Jones
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Dafni
authors.initials: D
authors.lastname: Moschidou
authors.affiliation: Institute of Orthopaedics and Musculoskeletal Science, Royal National Orthopaedic Hospital, University College London, Stanmore, UK.
authors.forename: Benan
authors.initials: B
authors.lastname: Dala-Ali
authors.affiliation: Institute of Orthopaedics and Musculoskeletal Science, Royal National Orthopaedic Hospital, University College London, Stanmore, UK.
authors.forename: Allen E
authors.initials: AE
authors.lastname: Goodship
authors.affiliation: UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: De Coppi
authors.affiliation: Department of Cell &Developmental Biology, University College London, London, UK.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Arnett
authors.affiliation: Institute for Women's Health, University College London, London, UK.
authors.forename: Pascale V
authors.initials: PV
authors.lastname: Guillot
mesh_terms: D000650:Amnion / Q000166:cytology*; D000818:Animals; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D050723:Fractures, Bone / Q000517:prevention & control*; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis; D010013:Osteogenesis Imperfecta / Q000517:prevention & control*; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D005819:Genetic Markers; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha