title: Implantation of rAAV5-IGF-I transduced autologous chondrocytes improves cartilage repair in full-thickness defects in the equine model.
abstract: Cartilage injury often precipitates osteoarthritis which has driven research to bolster repair in cartilage impact damage. Autologous chondrocytes transduced with rAAV5-IGF-I were evaluated in chondral defects in a well-established large animal model. Cartilage was harvested from the talus of 24 horses; chondrocytes were isolated and stored frozen. Twenty million cells were cultured and transduced with 10(5) AAV vg/cell prior to implantation. Chondrocytes from eight horses were transduced with rAAV5-IGF-I, chondrocytes from eight horses with rAAV5-GFP, and chondrocytes from eight horses were not transduced. A 15 mm full-thickness chondral defect was created arthroscopically in the lateral trochlear ridge of the femur in both femoropatellar joints. Treated defects were filled with naive or gene-enhanced chondrocytes, in fibrin vehicle. Control defects in the opposite limb received fibrin alone. rAAV5-IGF-I transduced chondrocytes resulted in significantly better healing at 8 week arthroscopy and 8 month necropsy examination when compared to controls. At 8 months, defects implanted with cells expressing IGF-I had better histological scores compared to control defects and defects repaired with naive chondrocytes. This included increased chondrocyte predominance and collagen type II, both features of hyaline-like repair tissue. The equine model closely approximates human cartilage healing, indicating AAV-mediated genetic modification of chondrocytes may be clinically beneficial to humans.
authors.affiliation: Comparative Orthopaedics Laboratory, Cornell University, Ithaca, New York, USA.
authors.forename: Kyla F
authors.initials: KF
authors.lastname: Ortved
authors.affiliation: Comparative Orthopaedics Laboratory, Cornell University, Ithaca, New York, USA.
authors.forename: Laila
authors.initials: L
authors.lastname: Begum
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
authors.forename: Hussni O
authors.initials: HO
authors.lastname: Mohammed
authors.affiliation: Comparative Orthopaedics Laboratory, Cornell University, Ithaca, New York, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Nixon
mesh_terms: D000818:Animals; D001182:Arthroscopy; D002358:Cartilage, Articular; D017690:Cell Transplantation; D019902:Chondrocytes / Q000378:metabolism* / Q000637:transplantation*; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006736:Horses; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D007592:Joint Diseases / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D012038:Regeneration; D013582:Synovial Fluid / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014945:Wound Healing
chemical_list: D007334:Insulin-Like Growth Factor I