Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7.
BACKGROUND
Cartilage has a limited capacity to heal. Although chondrocyte transplantation is a useful therapeutic strategy, the repair process can be lengthy. Previously we have shown that over expression of bone morphogenetic protein-7 (BMP-7) in chondrocytes by adenovirus-mediated gene transfer leads to increased matrix synthesis and cartilage-like tissue formation in vitro. In this context we hypothesized that implantation of genetically modified chondrocytes expressing BMP-7 would accelerate the formation of hyaline-like repair tissue in an equine model of cartilage defect repair.


METHODS
Chondrocytes treated with adenovirus vector encoding BMP-7 (AdBMP-7) or as control, an adenovirus vector encoding an irrelevant gene (Escherichia coli cytosine deaminase, AdCD) were implanted into extensive (15 mm diameter) articular cartilage defects in the patellofemoral joints of 10 horses. Biopsies were performed to evaluate early healing at 4 weeks. At the terminal time point of 8 months, repairs were assessed for morphology, MRI appearance, compressive strength, biochemical composition and persistence of implanted cells.


RESULTS
Four weeks after surgery AdBMP-7-treated repairs showed an increased level of BMP-7 expression and accelerated healing, with markedly more hyaline-like morphology than control. Quantitative real-time polymerase chain reaction (PCR) analysis of the repair tissue 8 months after surgery showed that few implanted cells persisted. By this time, the controls had healed similarly to the AdBMP-7-treated defects, and no difference was detected in the morphologic, biochemical or biomechanical properties of the repair tissues from the two treatment groups.


CONCLUSIONS
Implantation of genetically modified chondrocytes expressing BMP-7 accelerates the appearance of hyaline-like repair tissue in experimental cartilage defects.


CONCLUSIONS
Rehabilitation after cell-based cartilage repair can be prolonged, leading to decreased patient productivity and quality of life. This study shows the feasibility of using genetically modified chondrocytes to accelerate cartilage healing.
Hidaka
Chisa
C
Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, NY 10021, USA.
Goodrich
Laurie R
LR
Chen
Chih-Tung
CT
Warren
Russell F
RF
Crystal
Ronald G
RG
Nixon
Alan J
AJ
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002356:Cartilage / Q000293:injuries* / Q000473:pathology; D002357:Cartilage Diseases / Q000473:pathology / Q000628:therapy* / Q000662:veterinary*; D019902:Chondrocytes / Q000502:physiology / Q000637:transplantation*; D019245:Compressive Strength; D004247:DNA / Q000032:analysis; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006085:Graft Survival; D006734:Horse Diseases / Q000473:pathology / Q000628:therapy; D006736:Horses; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D011859:Radiography; D013582:Synovial Fluid; D016212:Transforming Growth Factor beta; D014945:Wound Healing
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D004247:DNA