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Chondrocyte Transplantation (chondrocyte + transplantation)
Selected AbstractsRepair of porcine articular cartilage defect with autologous chondrocyte transplantationJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2005Hongsen Chiang Abstract Articular cartilage is known to have poor healing capacity after injury. Autologous chondral grafting remains the mainstay to treat well-defined, full-thickness, symptomatic cartilage defects. We demonstrated the utilization of gelatin microbeads to deliver autologous chondrocytes for in vivo cartilage generation. Chondrocytes were harvested from the left forelimbs of 12 Lee-Sung pigs. The cells were expanded in monolayer culture and then seeded onto gelatin microbeads or left in monolayer. Shortly before implantation, the cell-laden beads were mixed with collagen type I gel, while the cells in monolayer culture were collected and re-suspended in culture medium. Full-thickness cartilage defects were surgically created in the weight-bearing surface of the femoral condyles of both knees, covered by periosteal patches taken from proximal tibia, and sealed with a porcine fibrin glue. In total, 48 condyles were equally allotted to experimental, control, and null groups that were filled beneath the patch with chondrocyte-laden beads in gel, chondrocytes in plain medium solution, or nothing, respectively. The repair was examined 6 months post-surgery on the basis of macroscopic appearance, histological scores based on the International Cartilage Repair Society Scale, and the proportion of characteristic chondrocytes. Tensile stress-relaxation behavior was determined from uniaxial indentation tests. The experimental group scored higher than the control group in the categories of matrix nature, cell distribution pattern, and absence of mineralization, with similar surface smoothness. Both the experimental and control groups were superior to the null group in the above-mentioned categories. Viable cell populations were equal in all groups, but the proportion of characteristic chondrocytes was highest in the experimental group. Matrix stiffness was ranked as null > native cartilage > control > experimental group. Transplanted autologous chondrocytes survive and could yield hyaline-like cartilage. The application of beads and gel for transplantation helped to retain the transferred cells in situ and maintain a better chondrocyte phenotype. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2003Chisa Hidaka 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. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Overexpression of human fibroblast growth factor 2 stimulates cell proliferation in an ex vivo model of articular chondrocyte transplantation,THE JOURNAL OF GENE MEDICINE, Issue 2 2004Henning Madry Abstract Background Genetically engineered chondrocytes could be used to enhance cartilage repair. Fibroblast growth factor 2 (FGF-2) is a mitogen for chondrocytes and may be a candidate for gene transfer approaches to stimulate chondrocyte proliferation. In the present study, we tested the hypothesis that human FGF-2 (hFGF-2) gene transfer into articular chondrocytes modulates cell proliferation in an ex vivo model of chondrocyte transplantation. Methods Transfection of articular chondrocytes with an expression plasmid vector carrying the cDNA for hFGF-2 under the control of the cytomegalovirus promoter/enhancer mediated transgene expression and synthesis of biologically relevant amounts of the recombinant hFGF-2 protein. Articular chondrocytes transfected with the Escherichia coli ,-galactosidase (lacZ) gene or a hFGF-2 cDNA were transplanted onto the surface of articular cartilage explants. Results The tissue formed by the chondrocytes expressing hFGF-2 was thicker and contained more cells than control cultures. Quantitative analysis of [3H]thymidine and [35S]sulfate incorporation in composite cultures revealed that hFGF-2 transfection stimulated mitogenic activity in the new tissue but did not augment matrix glycosaminoglycan synthesis. Conclusions These data support the concept that chondrocytes overexpressing a hFGF-2 cDNA selectively modulate cell proliferation in an ex vivo model of chondrocyte transplantation. These results suggest that therapeutic hFGF-2 gene transfer may be applicable for the treatment of articular cartilage disorders, such as traumatic defects in which cellular repopulation is a therapeutic goal. Copyright © 2004 John Wiley & Sons, Ltd. [source] Potential of Fortified Fibrin/Hyaluronic Acid Composite Gel as a Cell Delivery Vehicle for ChondrocytesARTIFICIAL ORGANS, Issue 6 2009Sang-Hyug Park Abstract Numerous treatment methods have been applied for use in cartilage repair, including abrasion, drilling, and microfracture. Although chondrocyte transplantation is the preferred treatment, it has some shortcomings, such as difficulty of application (large and posterior condylar regions), poor chondrocyte distribution, and potential cell leakage from the defect region. The cell delivery system of the tissue engineering technique can be used to overcome these shortcomings. We chose fibrin/hyaluronan (HA) composite gel as an effective cell delivery system to resolve these issues. Both components are derived from natural extracellular matrix. In the first trial, fortified fibrin/HA composite gels with rabbit chondrocytes were tested by implantation in nude mice. At 4 weeks, glycosaminoglycan contents in the fibrin/HA composite (0.186 ± 0.006 mg/mg) were significantly higher than those in the presence of fibrin alone (0.153 ± 0.017 mg/mg). As a next step, we applied the fibrin/HA composite gel to animal cartilage defects using full thickness cartilage defect rabbit models. The fibrin/HA composite gel with rabbit chondrocytes (allogenic) was implanted into the experimental group, and the control group was implanted with the fibrin/HA composite gel alone. Implanted chondrocytes with the fibrin/HA composite showed improved cartilage formation. In conclusion, the key to successful regeneration of cartilage is to provide the repair site with a sufficient supply of chondrogenic cells with a suitable delivery vehicle to ensure maximal differentiation and deposition of the proper extracellular matrix. This study suggests the feasibility of tissue-engineered cartilage formation using fibrin/HA composite gel. [source] | ||||||||||