title: Effects of transforming growth factor-beta1 and vascular endothelial growth factor 165 gene transfer on Achilles tendon healing.
abstract: Repaired Achilles tendons typically take weeks before they are strong enough to handle physiological loads. Gene therapy is a promising treatment for Achilles tendon defects. The aim of the present study was to evaluate the histological/biomechanical effects of Transforming growth factor-beta1 (TGF-beta1) and vascular endothelial growth factor 165 (VEGF(165)) gene transfer on Achilles tendon healing in rabbits. Bone Marrow-Derived Mesenchymal Stem Cells (BMSCs) were transduced with adenovirus carrying human TGF-beta1 cDNA (Ad-TGF-beta1), human VEGF(165) cDNA (Ad-VEGF(165)), or both (PIRES-TGF-beta1/VEGF(165)) Viruses, no cDNA (Ad-GFP), and the BMSCs without gene transfer and the intact tendon were used as control. BMSCs were surgically implanted into the experimentally injured Achilles tendons. TGF-beta1 distribution, cellularity, nuclear aspect ratio, nuclear orientation angle, vascular number, collagen synthesis, and biomechanical features were measured at 1, 2, 4, and 8 weeks after surgery. The TGF-beta1 and TGF beta 1/VEGF(165) co-expression groups exhibited improved parameters compared with other groups, while the VEGF(165) expression group had a negative impact. In the co-expression group, the angiogenesis effects of VEGF(165) were diminished by TGF-beta1, while the collagen synthesis effects of TGF-beta1 were unaltered by VEGF(165). Thus treatment with TGF-beta1 cDNA-transduced BMSCs grafts is a promising therapy for acceleration and improvement of tendon healing, leading to quicker recovery and improved biomechanical properties of Achilles tendons.
authors.affiliation: Institute of Sports Medicine, Peking University, Third Hospital, 49 North Garden Road, Haidian District, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hou
authors.forename: ZeBin
authors.initials: Z
authors.lastname: Mao
authors.forename: XueLei
authors.initials: X
authors.lastname: Wei
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: LianXu
authors.initials: L
authors.lastname: Chen
authors.forename: HaiJun
authors.initials: H
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Fu
authors.forename: JiYing
authors.initials: J
authors.lastname: Zhang
authors.forename: Changlong
authors.initials: C
authors.lastname: Yu
mesh_terms: D000125:Achilles Tendon / Q000033:anatomy & histology / Q000502:physiology*; D000818:Animals; D001696:Biomechanical Phenomena; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D011817:Rabbits; D012038:Regeneration / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A