Biochemical studies on repair cartilage resurfacing experimental defects in the rabbit knee.

Furukawa, Tomonari; Eyre, David R.; Koide, S; Glimcher, M J

doi:10.2106/00004623-198062010-00012

Cited by 438 publications

(240 citation statements)

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“…2,4,5,[30][31][32][33] It is important to note that there is insufficient intrinsic healing of the defects in this model system, as evidenced by the high (abnormal) score values in the lacZ control group at both time points. We have previously demonstrated that recombinant genes can be introduced into osteochondral defects in vivo by transfected articular chondrocytes in alginate and that transgene expression remains present in vivo for at least 32 days post transfection.…”

Section: Discussionmentioning

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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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: Discussionmentioning

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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“…Some of the approaches being used clinically to regenerate cartilage include drilling of articular defects to recruit stem cells from the subchondral bone to participate in repair, mosaic-plasty, and autologous chondrocyte transplantation [1][2][3]. All these approaches, however, have inherent problems in that they cannot repair cartilage full-thickness defects and also there may be morbidity-associated problems and possible disease transmission [2,4,5].…”

Section: Introductionmentioning

confidence: 99%

Adenoviral-mediated transfer of TGF-β1 but not IGF-1 induces chondrogenic differentiation of human mesenchymal stem cells in pellet cultures

Kawamura¹,

Chu²,

Sobajima³

et al. 2005

Experimental Hematology

102

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Objective. The objective of the present study was to investigate the potential of application of growth factor genes to induce chondrogenic differentiation of human-derived mesenchymal stem cells (MSCs). The growth factor genes evaluated in the present study were transforming growth factor 1 (TGF-β1) and insulin-like growth factor 1 (IGF-1).Methods. Human MSCs were transduced with the adenoviral vectors carrying either TGF-β1 or IGF-1 (AdTGF-β1 and AdIGF-1 respectively) or a combination of both growth factor genes at different multiplicities of infection (MOI) and were then made into pellets. Pellets were also made from nontransduced cells and maintained in culture medium supplemented with 10 ng/mL of TGF-β1. At specified time points, histological analysis, cartilage matrix gene expression, and immunofluorescence were performed to determine the extent of chondrogenic differentiation.Results. MSCs transduced with the AdTGF-β1 demonstrated robust chondrogenic differentiation, while those made from AdIGF-1 did not. AdTGF-β1 pellets demonstrated aggrecan gene expression as early as day 3 of pellet culture, while type II collagen gene expression was detected by day 10 of culture. The AdIGF-1, alone or in combination with TGF-β1 pellets, did not show any type II collagen gene expression at any time point. By immunofluoresecence, type X collagen was distributed throughout the matrix in TGF-β1 protein pellets while the growth factor gene pellets displayed scant staining. Conclusion.The results suggest that sustained administration of TGF-β1 may be more effective in suppressing terminal differentiation than intermittent dosing and thus effective for cartilage repair.

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“…The success rates with these treatments vary greatly. While some of these approaches show promise, many lead to formation of fibrous tissue, apoptosis, and further cartilage degeneration (1)(2)(3)(4)(5)(6). To address the need for improved therapies to promote cartilage repair or regeneration, a number of novel tissue engineering approaches have been developed for the treatment of cartilage defects or osteoarthritis.…”

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confidence: 99%

Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

Estes

Guilak

2006

Arthritis & Rheumatism

271

212

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Objective. Recent studies have identified an abundant source of multipotent progenitor cells in subcutaneous human adipose tissue, termed human adiposederived adult stem cells (ADAS cells). In response to specific media formulations, including transforming growth factor ␤1 (TGF␤1), these cells exhibit significant ability to differentiate into a chondrocyte-like phenotype, expressing cartilage-specific genes and proteins such as aggrecan and type II collagen. However, the influence of other growth factors on the chondrogenic differentiation of ADAS cells is not fully understood. This study was undertaken to investigate the effects of TGF␤1, TGF␤3, insulin-like growth factor 1, bone morphogenetic protein 6 (BMP-6), and dexamethasone, in various combinations, on the chondrogenic potential of ADAS cells in alginate beads.Methods. The chondrogenic response of alginateencapsulated ADAS cells was measured by quantitative polymerase chain reaction, 3 H-proline and 35 S-sulfate incorporation, and immunolabeling for specific extracellular matrix components.Results. Significant differences in chondrogenesis were observed under the different culture conditions for all outcomes measured. Most notably, BMP-6 upregulated AGC1 and COL2A1 expression by an average of 205-fold and 38-fold, respectively, over day-0 controls, while down-regulating COL10A1 expression by ϳ2-fold.Conclusion. These findings suggest that BMP-6 is a potent inducer of chondrogenesis in ADAS cells, in contrast to mesenchymal stem cells, which exhibit increased expression of type X collagen and a hypertrophic phenotype in response to BMP-6. Combinations of growth factors containing BMP-6 may provide a novel means of regulating the differentiation of ADAS cells for applications in the tissue-engineered repair or regeneration of articular cartilage.

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Biochemical studies on repair cartilage resurfacing experimental defects in the rabbit knee.

Cited by 438 publications

References 0 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)

Adenoviral-mediated transfer of TGF-β1 but not IGF-1 induces chondrogenic differentiation of human mesenchymal stem cells in pellet cultures

Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6

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