Cartilage and Bone Regeneration Using Gene-Enhanced Tissue Engineering

Mason, James; Breitbart, Arnold S.; Barcia, Michele; Porti, Debra; Pergolizzi, Robert G.; Grande, Daniel

doi:10.1097/00003086-200010001-00023

Cited by 182 publications

(113 citation statements)

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“…Following positive selection and expansion in culture, the modified cells were seeded into bioresorbable polymer scaffolds, which were later implanted into osteochondral defects in allogenic rabbits. 96 Relative to control groups, rabbits receiving the grafts with cells expressing BMP-7 showed improved regeneration of bone and cartilage at 8 and 12 weeks postimplant. In an extension of this work, the authors recently compared delivery of the cDNA for sonic hedgehog and BMP-7 using the same experimental approach.…”

Section: Gene Transfer To Chondroprogenitor Cellsmentioning

confidence: 94%

Gene-based approaches for the repair of articular cartilage

2004

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Section: Gene Transfer To Chondroprogenitor Cellsmentioning

confidence: 94%

Gene-based approaches for the repair of articular cartilage

2004

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“…22 Preclinical studies of gene transfer for cartilage repair have typically favored ex vivo approaches because they deliver chondrogenic cells and their expressed gene products to the defect site. In this regard, chondrocytes, periosteal cells and MSCs have been tested as vehicles for gene delivery in animal models, [23][24][25][26][27] and while there has been evidence of cartilage repair, clinical application would require harvesting and culturing of autologous cells for each patient. From our clinical experience with ex vivo gene delivery to joints, it has become evident that the facilities, labor, time and, therefore, expense of these procedures may make this approach impractical for mainstream application.…”

Section: Introductionmentioning

confidence: 99%

Gene delivery to cartilage defects using coagulated bone marrow aspirate

et al. 2004

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The long-term goal of the present study is to develop a clinically applicable approach to enhance natural repair mechanisms within cartilage lesions by targeting bone marrow-derived cells for genetic modification. To determine if bone marrow-derived cells infiltrating osteochondral defects could be transduced in situ, we implanted collagen-glycosaminoglycan (CG) matrices preloaded with adenoviral vectors containing various marker genes into lesions surgically generated in rabbit femoral condyles. Analysis of the recovered implants showed transgenic expression up to 21 days; however, a considerable portion was found in the synovial lining, indicating leakage of the vector and/or transduced cells from the matrix. As an alternative medium for gene delivery, we investigated the feasibility of using coagulated bone marrow aspirates. Mixture of an adenoviral suspension with the fluid phase of freshly aspirated bone marrow resulted in uniform dispersion of the vector throughout, and levels of transgenic expression in direct proportion to the density of nucleated cells in the ensuing clot. Furthermore, cultures of mesenchymal progenitor cells, previously transduced ex vivo with recombinant adenovirus, were readily incorporated into the coagulate when mixed with fresh aspirate. These vector-seeded and cell-seeded bone marrow clots were found to maintain their structural integrity following extensive culture and maintained transgenic expression in this manner for several weeks. When used in place of the CG matrix as a gene delivery vehicle in vivo, genetically modified bone marrow clots were able to generate similarly high levels of transgenic expression in osteochondral defects with better containment of the vector within the defect. Our results suggest that coagulates formed from aspirated bone marrow may be useful as a means of gene delivery to cartilage and perhaps other musculoskeletal tissues. Cells within the fluid can be readily modified with an adenoviral vector, and the matrix formed from the clot is completely natural, native to the host and is the fundamental platform on which healing and repair of mesenchymal tissues is based.

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“…The newly formed tissues integrated well with the host cartilage, indicating that the remodelling of the cartilage matrix is stimulated by the recombinant OP-1 [16,18]. A study by Mason et al reported the use of a combined gene therapy and tissue engineering approach to repair articular cartilage defects in rabbits [25], and complete or near complete regeneration of the bone and cartilage was seen in the grafts containing the OP-1 modified cells, compared to poor repair by the control grafts [25].…”

Section: Introductionmentioning

confidence: 95%

“…The repair of articular cartilage defects in vivo using rhOP-1 has been reported in rabbits, goats, sheep and dogs [4,11,16,24,25]. The defect is repaired through the infiltration of mesenchymal cells that differentiate into cells resembling articular cartilage chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

The effect of recombinant human osteogenic protein-1 on growth plate repair in a sheep model

et al. 2005

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Injuries to the growth plate in children can result in bone bridge formation, which ultimately lead to limb length and angular deformities. The histological and molecular changes associated with growth plate repair following the Langenskiold procedure, a surgical technique used to remove impeding bone bridges, in conjunction with administration of recombinant human osteogenic protein-1 (rhOP-1) were examined using a sheep model. Following treatment with rhOP-1 there was an increase in the'height of the growth plate immediately adjacent to the defect compared to untreated animals. The expression of type I collagen, osteopontin and decorin were observed in the growth plate adjacent to the defect in the untreated animals at day 56, but this response was accelerated in the rhOP-1 treated animals, with these molecules seen as early as day 7. Therefore, treatment with rhOP-1 initiated a complex response that was both chondrogenic and osteogenic in nature.

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Cartilage and Bone Regeneration Using Gene-Enhanced Tissue Engineering

Cited by 182 publications

References 0 publications

Gene-based approaches for the repair of articular cartilage

Gene-based approaches for the repair of articular cartilage

Gene delivery to cartilage defects using coagulated bone marrow aspirate

The effect of recombinant human osteogenic protein-1 on growth plate repair in a sheep model

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