Articular cartilage repair by genetically modified bone marrow aspirate in sheep.
Bone marrow presents an attractive option for the treatment of articular cartilage defects as it is readily accessible, it contains mesenchymal progenitor cells that can undergo chondrogenic differentiation and, once coagulated, it provides a natural scaffold that contains the cells within the defect. This study was performed to test whether an abbreviated ex vivo protocol using vector-laden, coagulated bone marrow aspirates for gene delivery to cartilage defects may be feasible for clinical application. Ovine autologous bone marrow was transduced with adenoviral vectors containing cDNA for green fluorescent protein or transforming growth factor (TGF)-beta1. The marrow was allowed to clot forming a gene plug and implanted into partial-thickness defects created on the medial condyle. At 6 months, the quality of articular cartilage repair was evaluated using histological, biochemical and biomechanical parameters. Assessment of repair showed that the groups treated with constructs transplantation contained more cartilage-like tissue than untreated controls. Improved cartilage repair was observed in groups treated with unmodified bone marrow plugs and Ad.TGF-beta1-transduced plugs, but the repaired tissue from TGF-treated defects showed significantly higher amounts of collagen II (P<0.001). The results confirmed that the proposed method is fairly straightforward technique for application in clinical settings. Genetically modified bone marrow clots are sufficient to facilitate articular cartilage repair of partial-thickness defects in vivo. Further studies should focus on selection of transgene combinations that promote more natural healing.
Ivkovic
A
A
Clinical Institute for Orthopaedic Aids and Rehabilitation, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia. aivkovic@inet.hr
Pascher
A
A
Hudetz
D
D
Maticic
D
D
Jelic
M
M
Dickinson
S
S
Loparic
M
M
Haspl
M
M
Windhager
R
R
Pecina
M
M
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation; D002358:Cartilage, Articular / Q000293:injuries*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D012756:Sheep; D014161:Transduction, Genetic; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014945:Wound Healing
D053773:Transforming Growth Factor beta1