title: Fluorescence molecular tomography enables in vivo visualization and quantification of nonunion fracture repair induced by genetically engineered mesenchymal stem cells.
abstract: Fluorescence molecular tomography (FMT) is a novel tomographic near-infrared (NIR) imaging modality that enables 3D quantitative determination of fluorochrome distribution in tissues of live small animals at any depth. This study demonstrates a noninvasive, quantitative method of monitoring engineered bone remodeling via FMT. Murine mesenchymal stem cells overexpressing the osteogenic gene BMP2 (mMSCs-BMP2) were implanted into the thigh muscle and into a radial nonunion bone defect model in C3H/HeN mice. Real-time imaging of bone formation was performed following systemic administration of the fluorescent bisphosphonate imaging agent OsteoSense, an hydroxyapatite-directed bone-imaging probe. The mice underwent imaging on days 7, 14, and 21 postimplantation. New bone formation at the implantation sites was quantified using micro-computed tomography (micro-CT) imaging. A higher fluorescent signal occurred at the site of the mMSC-BMP2 implants than that found in controls. Micro-CT imaging revealed a mass of mature bone formed in the implantation sites on day 21, a finding also confirmed by histology. These findings highlight the effectiveness of FMT as a functional platform for molecular imaging in the field of bone regeneration and tissue engineering.
authors.affiliation: Skeletal Biotechnology Laboratory, Hebrew University, Hadassah Medical Campus, P.O. Box 12272, Ein Kerem, Jerusalem 91120, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Zilberman
authors.forename: Ilan
authors.initials: I
authors.lastname: Kallai
authors.forename: Yossi
authors.initials: Y
authors.lastname: Gafni
authors.forename: Gadi
authors.initials: G
authors.lastname: Pelled
authors.forename: Sylvie
authors.initials: S
authors.lastname: Kossodo
authors.forename: Wael
authors.initials: W
authors.lastname: Yared
authors.forename: Dan
authors.initials: D
authors.lastname: Gazit
mesh_terms: D000818:Animals; D005260:Female; D005456:Fluorescent Dyes; D017102:Fracture Healing / Q000502:physiology*; D005599:Fractures, Ununited / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D005818:Genetic Engineering; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D010012:Osteogenesis / Q000502:physiology*; D011885:Radius Fractures / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D014057:Tomography, X-Ray Computed
chemical_list: D005456:Fluorescent Dyes