Bone morphogenetic protein-transduced human fibroblasts convert to osteoblasts and form bone in vivo.
Experimental cell or ex vivo gene therapy for localized bone formation typically uses osteoprogenitor cells propagated from periosteum or bone marrow. Both require bone or marrow biopsies to obtain cells. We have demonstrated that implantation of gingival or dermal fibroblasts transduced with BMP ex vivo, using a recombinant adenovirus (AdCMVBMP) attached to porous biodegradable scaffolds, form bone in vivo. Here we show that BMP-7-transduced fibroblasts suspended in injectable thermoset hydrogels form complete ossicles on subcutaneous injection and repair segmental defects in rat femurs. Bone formation was preceded by an intermediate cartilage stage. To determine the fate of the implanted transduced cells, thermoset hydrogel suspensions of ex vivo BMP-7-transduced or nontransduced fibroblasts were placed in diffusion chambers and implanted to allow development in vivo without direct contact with host cells. Only the BMP-transduced fibroblasts formed bone within the diffusion chambers in vivo, revealing that BMP transduction induces osteoblastic conversion of these cells.
Rutherford
R Bruce
RB
School of Dentistry, Center for Biorestoration of Oral Health, University of Michigan, 1011 N. University, Ann Arbor, MI 48109-1078, USA.
Moalli
Maria
M
Franceschi
Renny T
RT
Wang
Dian
D
Gu
Keni
K
Krebsbach
Paul H
PH
D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000502:physiology; D001861:Bone Regeneration / Q000235:genetics / Q000502:physiology; D002356:Cartilage / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation; D017690:Cell Transplantation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D006801:Humans; D020100:Hydrogels; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics* / Q000502:physiology; D051381:Rats; D023822:Tissue Engineering; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta
C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D020100:Hydrogels; D016212:Transforming Growth Factor beta