Repair of Partial-Thickness Defects in Articular Cartilage

Hunziker, Ernst B.; Rosenberg, Lawrence

doi:10.2106/00004623-199605000-00012

Cited by 602 publications

(394 citation statements)

References 46 publications

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“…Adapted from Sellers et al 4,5 Enhanced cartilage repair by IGF-I overexpression H Madry et al relatively large, often repeated, doses of growth factors. [2][3][4][5][6]10 This is consistent with a relatively rapid clearance of otherwise potent therapeutic molecules and suggests a value for local growth factor production. Gene therapy at the site of articular cartilage repair is a clinically relevant application of gene transfer technology and represents a potential solution to these problems.…”

Section: Discussionsupporting

confidence: 65%

“…When cell-based therapy is employed, there arises the additional challenge of retaining the transplanted cells in the defect. 1 The initial healing response to an osteochondral articular cartilage defect is mediated, in part, by cell signaling polypeptides that act on cells derived either from the joint cavity 2 or the bone marrow. 3 Such polypeptides influence the rate of articular cartilage repair.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I)

et al. 2005

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Traumatic articular cartilage lesions have a limited capacity to heal. We tested the hypothesis that overexpression of a human insulin-like growth factor I (IGF-I) cDNA by transplanted articular chondrocytes enhances the repair of fullthickness (osteochondral) cartilage defects in vivo. Lapine articular chondrocytes were transfected with expression plasmid vectors containing the cDNA for the Escherichia coli lacZ gene or the human IGF-I gene and were encapsulated in alginate. The expression patterns of the transgenes in these implants were monitored in vitro for 36 days. Transfected allogeneic chondrocytes in alginate were transplanted into osteochondral defects in the trochlear groove of rabbits. At three and 14 weeks, the quality of articular cartilage repair was evaluated qualitatively and quantitatively. In vitro, IGF-I secretion by implants constructed from IGF-I-transfected chondrocytes and alginate was 123.2722.3 ng/10 7 cells/24 h at day 4 post transfection and remained elevated at day 36, the longest time point evaluated. In vivo, transplantation of IGF-I implants improved articular cartilage repair and accelerated the formation of the subchondral bone at both time points compared to lacZ implants. The data indicate that allogeneic chondrocytes, transfected by a nonviral method and cultured in alginate, are able to secrete biologically relevant amounts of IGF-I over a prolonged period of time in vitro. The data further demonstrate that implantation of these composites into deep articular cartilage defects is sufficient to augment cartilage defect repair in vivo. These results suggest that therapeutic growth factor gene delivery using encapsulated and transplanted genetically modified chondrocytes may be applicable to sites of focal articular cartilage damage.

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Section: Discussionsupporting

confidence: 65%

Section: Introductionmentioning

confidence: 99%

Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I)

et al. 2005

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“…Although the origin of these stem cells in the joint is unknown, their presence in the normal synovium has also been demonstrated in humans and in rabbits, where TGFb stimulation was shown to induce cartilage tissue formation. 32,35 Engineering MSCs MSCs can be used in different therapeutic strategies either as immunosuppressive agents or genetically engineered to express molecules acting against the autoimmune process. As MSCs are not rejected and traffic to injuried mesenchymal tissues, in particular bone, they represent the opportunity to deliver therapeutic proteins.…”

Section: Hematopoietic and Mscs In Autoimmune Diseasesmentioning

confidence: 99%

Engineering mesenchymal stem cells for immunotherapy

et al. 2003

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“…Also, osteophytes occurring due to osteoarthritis are usually accompanied by excess cartilage formation and are commonly observed at the synovium-cartilage junction (37). In addition, when partial-thickness defects in the articular cartilage of rabbits were formed, a continuous layer extending from the synovial membrane, which contributed to the repair of the cartilage, was observed (38). Furthermore, free synovial grafts contributed to the healing process in the avascular zone of torn menisci in rabbits (39).…”

mentioning

confidence: 99%

Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source

Sakaguchi¹,

Sekiya²,

Yagishita³

et al. 2005

Arthritis & Rheumatism

1,375

1,171

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Objective. To compare the properties of human mesenchymal stem cells (MSCs) isolated from bone marrow, synovium, periosteum, skeletal muscle, and adipose tissue.Methods. Human mesenchymal tissues were obtained from 8 donors during knee surgery for ligament injury. After collagenase digestion or gradient-density separation, nucleated cells were plated at an appropriate density for expansion at the maximum rate without colony-to-colony contact. Yield, expandability, differentiation potential, and epitope profile were compared among MSCs from the 5 different tissue sources.Results. Colony number per 10 3 nucleated cells was lower, and cell number per colony was higher, in bone marrow than in other mesenchymal tissues. When the cells were replated at low density every 14 days, bone marrow-, synovium-, and periosteum-derived cells retained their proliferation ability even at passage 10. In chondrogenesis studies in which the cells were pelleted and cultured in vitro, pellets from bone marrow-, synovium-, and periosteum-derived cells were shown to be larger and stained more extensively for cartilage matrix. Synovium-derived cells, in particular, had the greatest ability for chondrogenesis. In adipogenesis experiments, the frequency of oil red O-positive colonies was highest in synovium-and adipose tissue-derived cells. In studies of osteogenesis, the rate of alizarin red-positive colonies was highest in bone marrow-, synovium-, and periosteum-derived cells. For epitope profiling, 15 surface antigens were measured. Most appeared to have similar epitope profiles irrespective of cell source.Conclusion. Our findings indicate that there are significant differences in MSC properties according to tissue source, beyond donor and experimental variation. Superiority of synovium as a potential source of MSCs for clinical applications was demonstrated.

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Repair of Partial-Thickness Defects in Articular Cartilage

Cited by 602 publications

References 46 publications

Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I)

Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I)

Engineering mesenchymal stem cells for immunotherapy

Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source

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