title: Autologous implantation of BMP2-expressing dermal fibroblasts to improve bone mineral density and architecture in rabbit long bones.
abstract: Cell-mediated gene therapy may treat bone fragility disorders. Dermal fibroblasts (DFb) may be an alternative cell source to stem cells for orthopedic gene therapy because of their rapid cell yield and excellent plasticity with bone morphogenetic protein-2 (BMP2) gene transduction. Autologous DFb or BMP2-expressing autologous DFb were administered in twelve rabbits by two delivery routes; a transcortical intra-medullar infusion into tibiae and delayed intra-osseous injection into femoral drill defects. Both delivery methods of DFb-BMP2 resulted in a successful cell engraftment, increased bone volume, bone mineral density, improved trabecular bone microarchitecture, greater bone defect filling, external callus formation, and trabecular surface area, compared to non-transduced DFb or no cells. Cell engraftment within trabecular bone and bone marrow tissue was most efficiently achieved by intra-osseous injection of DFb-BMP2. Our results suggested that BMP2-expressing autologous DFb have enhanced efficiency of engraftment in target bones resulting in a measurable biologic response by the bone of improved bone mineral density and bone microarchitecture. These results support that autologous implantation of DFb-BMP2 warrants further study on animal models of bone fragility disorders, such as osteogenesis imperfecta and osteoporosis to potentially enhance bone quality, particularly along with other gene modification of these diseases.
authors.affiliation: Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, Ohio.
authors.forename: Akikazu
authors.initials: A
authors.lastname: Ishihara
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Weisbrode
authors.affiliation: Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, Ohio.|Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio.
authors.forename: Alicia L
authors.initials: AL
authors.lastname: Bertone
mesh_terms: D000818:Animals; D015519:Bone Density; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D001842:Bone and Bones / Q000033:anatomy & histology; D002454:Cell Differentiation; D017690:Cell Transplantation / Q000379:methods; D005347:Fibroblasts / Q000378:metabolism / Q000637:transplantation*; D010012:Osteogenesis; D011817:Rabbits; D011897:Random Allocation; D012867:Skin / Q000166:cytology; D014182:Transplantation, Autologous
chemical_list: D055396:Bone Morphogenetic Protein 2
keywords: autologous implantation; bone morphogenetic protein-2; dermal fibroblasts; intra-medullar cell delivery; intra-osseous cell delivery