Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7

Chisa Hidaka, Laurie R. Goodrich, Chih Tung Chen, Russell F. Warren, Ronald G. Crystal, Alan J. Nixon

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)573-583
Number of pages11
JournalJournal of Orthopaedic Research
Volume21
Issue number4
DOIs
StatePublished - 2003

Fingerprint

Bone Morphogenetic Protein 7
Chondrocytes
Cartilage
Adenoviridae
Hyalin
Horses
Cytosine Deaminase
Patellofemoral Joint
Compressive Strength
Feasibility Studies
Articular Cartilage
Genes
Real-Time Polymerase Chain Reaction
Rehabilitation
Transplantation
Quality of Life
Escherichia coli
Biopsy
Therapeutics

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7. / Hidaka, Chisa; Goodrich, Laurie R.; Chen, Chih Tung; Warren, Russell F.; Crystal, Ronald G.; Nixon, Alan J.

In: Journal of Orthopaedic Research, Vol. 21, No. 4, 2003, p. 573-583.

Research output: Contribution to journalArticle

Hidaka, Chisa ; Goodrich, Laurie R. ; Chen, Chih Tung ; Warren, Russell F. ; Crystal, Ronald G. ; Nixon, Alan J. / Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7. In: Journal of Orthopaedic Research. 2003 ; Vol. 21, No. 4. pp. 573-583.
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abstract = "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.",
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