title: Bone formation following OP-1 implantation is improved by addition of autogenous bone marrow cells in a canine femur defect model.
abstract: Osteogenic Protein-1 (OP-1, BMP-7) acts locally on connective tissue progenitors (CTPs) to induce bone formation. The response to OP-1 and similar agents is potentially limited by the number of local CTPs. This study tested the hypothesis that supplementing local CTPs using autogenous bone marrow will enhance bone formation at an OP-1 implant. Four 1.0-cm diameter unicortical cylindrical defects in the left proximal femur were grafted in each of seven dogs. Radial ingrowth of new bone formation was assessed at 4 weeks using micro CT. The OP-1 (3.5 mg rhOP-1 in 1 g bovine collagen I matrix) was implanted in each site combined with either clotted blood or aspirated bone marrow (BM). Bone formation was increased in the group augmented with transplanted marrow. These data suggest that increasing the local population of cells and CTPs using aspirated bone marrow can enhance the performance of OP-1, but may not eliminate the effects of site variation on the response to OP-1 and similar agents. The canine multiple femoral defect model defined in this study is well suited to quantitatively evaluate strategies for augmenting bone repair using local cell targeting and cell transplantation strategies.
authors.affiliation: Department of Biomedical Engineering, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.
authors.forename: Hidetake
authors.initials: H
authors.lastname: Takigami
authors.forename: Ken
authors.initials: K
authors.lastname: Kumagai
authors.forename: Larry
authors.initials: L
authors.lastname: Latson
authors.forename: Daisuke
authors.initials: D
authors.lastname: Togawa
authors.forename: Thomas
authors.initials: T
authors.lastname: Bauer
authors.forename: Kimerly
authors.initials: K
authors.lastname: Powell
authors.forename: Robert S
authors.initials: RS
authors.lastname: Butler
authors.forename: George F
authors.initials: GF
authors.lastname: Muschler
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004285:Dogs; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D005269:Femur / Q000000981:diagnostic imaging / Q000293:injuries / Q000601:surgery; D017102:Fracture Healing / Q000187:drug effects*; D020007:Implants, Experimental; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D010027:Osteotomy; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*
chemical_list: D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta