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. CLINICAL RELEVANCE: 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.
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. CLINICAL RELEVANCE: 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.
Authors: Hiromu Ito; Mette Koefoed; Prarop Tiyapatanaputi; Kirill Gromov; J Jeffrey Goater; Jonathan Carmouche; Xinping Zhang; Paul T Rubery; Joseph Rabinowitz; R Jude Samulski; Takashi Nakamura; Kjeld Soballe; Regis J O'Keefe; Brendan F Boyce; Edward M Schwarz Journal: Nat Med Date: 2005-02-13 Impact factor: 53.440
Authors: K A Payne; H H Lee; A M Haleem; C Martins; Z Yuan; C Qiao; X Xiao; C R Chu Journal: Osteoarthritis Cartilage Date: 2011-04-28 Impact factor: 6.576
Authors: James Melrose; Susan M Smith; Christopher B Little; Robert J Moore; Barrie Vernon-Roberts; Robert D Fraser Journal: Eur Spine J Date: 2008-06-27 Impact factor: 3.134
Authors: Laurie R Goodrich; Albert C Chen; Natasha M Werpy; Ashley A Williams; John D Kisiday; Alvin W Su; Esther Cory; Paul S Morley; C Wayne McIlwraith; Robert L Sah; Constance R Chu Journal: J Bone Joint Surg Am Date: 2016-01-06 Impact factor: 5.284
Authors: Vincent Y Ng; Seth S Jump; Kelly S Santangelo; Duncan S Russell; Alicia L Bertone Journal: Clin Orthop Relat Res Date: 2012-09-25 Impact factor: 4.176
Authors: Andre F Steinert; Benedikt Proffen; Manuela Kunz; Christian Hendrich; Steven C Ghivizzani; Ulrich Nöth; Axel Rethwilm; Jochen Eulert; Christopher H Evans Journal: Arthritis Res Ther Date: 2009-10-02 Impact factor: 5.156