title: Fibroblast growth factor-2 and vascular endothelial growth factor mediated augmentation of angiogenesis and bone formation in vascularized bone allotransplants.
abstract: We previously demonstrated recipient-derived neoangiogenesis to maintain viability of living bone allogeneic transplants without long-term immunosuppression. The effect of cytokine delivery to enhance this process is studied. Vascularized femur transplantation was performed from Dark Agouti to Piebald Virol Glaxo rats. Poly(d,l-lactide-co-glycolide) microspheres loaded with buffer (N = 11), basic fibroblast growth factor (FGF2) (N = 10), vascular endothelial growth factor (VEGF) (N = 11), or both (N = 11) were inserted intramedullarly alongside a recipient-derived arteriovenous bundle. FK-506 was administered for 2 weeks. At 18 weeks, bone blood flow, microangiography, histologic, histomorphometric, and alkaline phosphatase measurements were performed. Bone blood flow was greater in the combined group than control and VEGF groups (P = 0.04). Capillary density was greater in the FGF2 group than in the VEGF and combined groups (P < 0.05). Bone viability, growth, and alkaline phosphatase activity did not vary significantly between groups. Neoangiogenesis in vascularized bone allotransplants is enhanced by angiogenic cytokine delivery, with results using FGF2 that are comparable to isotransplant from previous studies. Further studies are needed to achieve bone formation similar to isotransplants.
authors.affiliation: Department of Orthopedic Surgery, Microvascular Research Laboratory, Mayo Clinic, Rochester, MN.
authors.forename: Mikko
authors.initials: M
authors.lastname: Larsen
authors.forename: Wouter F
authors.initials: WF
authors.lastname: Willems
authors.forename: Michael
authors.initials: M
authors.lastname: Pelzer
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Friedrich
authors.forename: Mahrokh
authors.initials: M
authors.lastname: Dadsetan
authors.forename: Allen T
authors.initials: AT
authors.lastname: Bishop
mesh_terms: D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D016025:Bone Transplantation; D001842:Bone and Bones / Q000098:blood supply; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010012:Osteogenesis; D051381:Rats; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2