title: Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons.
abstract: Tendon injury during limb motion is common. Damaged tendons heal poorly and frequently undergo unpredictable ruptures or impaired motion due to insufficient innate healing capacity. By basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) gene therapy via adeno-associated viral type-2 (AAV2) vector to produce supernormal amount of bFGF or VEGF intrinsically in the tendon, we effectively corrected the insufficiency of the tendon healing capacity. This therapeutic approach (1) resulted in substantial amelioration of the low growth factor activity with significant increases in bFGF or VEGF from weeks 4 to 6 in the treated tendons (p < 0.05 or p < 0.01), (2) significantly promoted production of type I collagen and other extracellular molecules (p < 0.01) and accelerated cellular proliferation, and (3) significantly increased tendon strength by 68-91% from week 2 after AAV2-bFGF treatment and by 82-210% from week 3 after AAV2-VEGF compared with that of the controls (p < 0.05 or p < 0.01). Moreover, the transgene expression dissipated after healing was complete. These findings show that the gene transfers provide an optimistic solution to the insufficiencies of the intrinsic healing capacity of the tendon and offers an effective therapeutic possibility for patients with tendon disunion.
authors: The Hand Surgery Research Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.|Department of Plastic Surgery, Rhode Island Hospital, The Alpert Medical School, Brown University, Providence, RI, USA.
authors: Jin Bo
authors: JB
authors: Tang
authors: The Hand Surgery Research Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors: Ya Fang
authors: YF
authors: Wu
authors: The Hand Surgery Research Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors: Yi
authors: Y
authors: Cao
authors: The Hand Surgery Research Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors: Chuan Hao
authors: CH
authors: Chen
authors: The Hand Surgery Research Center, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
authors: You Lang
authors: YL
authors: Zhou
authors: Department of Plastic Surgery, Rhode Island Hospital, The Alpert Medical School, Brown University, Providence, RI, USA.
authors: Bella
authors: B
authors: Avanessian
authors: Department of Molecular Biodefense Research, Yokohama City University, Yokohama, Japan.
authors: Masaru
authors: M
authors: Shimada
authors: Department of Plastic Surgery, Rhode Island Hospital, The Alpert Medical School, Brown University, Providence, RI, USA.|Surgical Research and Gene Therapy Research, Department of Surgery, Roger Williams Medical Center, Boston University School of Medicine, Boston, MA, USA.
authors: Xiao Tian
authors: XT
authors: Wang
authors: Department of Plastic Surgery, Rhode Island Hospital, The Alpert Medical School, Brown University, Providence, RI, USA.
authors: Paul Y
authors: PY
authors: Liu
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002645:Chickens; D024042:Collagen Type I / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D005353:Fibronectins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D007797:Laminin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D013708:Tendon Injuries / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D013710:Tendons / Q000378:metabolism / Q000473:pathology; D000070916:Tenocytes / Q000166:cytology / Q000378:metabolism; D013718:Tensile Strength; D019076:Transgenes; D042461:Vascular Endothelial Growth Factor A / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics*
chemical_list: D024042:Collagen Type I; D005353:Fibronectins; D007797:Laminin; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2