title: Treatment of osteonecrosis of the femoral head with VEGF165 transgenic bone marrow mesenchymal stem cells in mongrel dogs.
abstract: We evaluated the efficacy of vascular endothelial growth factor 165 (VEGF(165)) transgenic bone marrow mesenchymal stem cells (BMSCs) for the repair of early-stage osteonecrosis of the femoral head (ONFH) in mature mongrel dogs. This animal model was surgically established by femoral neck osteotomy and subsequent repinning. Twenty-seven dogs (54 hips) were divided into 3 equal-sized groups: a pCI-neo-VEGF(165) BMSC group, a pCI-neo BMSC group and a core decompression-alone group. The lipofectamine was used to introduce the VEGF(165) gene into the BMSCs. After core decompression, transgenic and non-transgenic autologous BMSCs were implanted. Therapeutic efficacy, including new bone formation and neovascularization in the femoral head, was examined by computed radiography, single-photon emission computed tomography, histological and histomorphometric analysis and immunofluorescent staining for von Willebrand factor in pathological sections. The femoral osteotomy site healed completely by the 4th week after the osteotomy surgery and regions of histologically evident osteonecrosis were found 12 weeks later. A regular arrangement of trabeculae and obvious bone regeneration were observed in the animals receiving implanted VEGF-transgenic BMSCs. The quantity of newly generated capillaries was significantly increased in the pCI-neo-VEGF(165) BMSC group, but there was no significant difference between the pCI-neo BMSC group and the core decompression-alone group. These results demonstrated that VEGF(165) transgenic autologous BMSCs enhanced bone reconstruction and blood vessel regeneration in the ONFH model. Compared with non-transgenic BMSCs, this approach could provide advanced benefits in the treatment of ONFH.
authors: Department of Orthopaedics, Zhongshan Hospital, Fudan University, Shanghai, PR China.
authors: Donghua
authors: D
authors: Hang
authors: Qiugen
authors: Q
authors: Wang
authors: Changan
authors: C
authors: Guo
authors: Zhengrong
authors: Z
authors: Chen
authors: Zuoqin
authors: Z
authors: Yan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001854:Bone Marrow Cells / Q000166:cytology*; D002453:Cell Cycle; D004247:DNA / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D005270:Femur Head / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D005271:Femur Head Necrosis / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D005434:Flow Cytometry; D015316:Genetic Therapy; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D018919:Neovascularization, Physiologic; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000627:therapeutic use*; D014945:Wound Healing
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004247:DNA