Effect of Cultured Autologous Chondrocytes on Repair of Chondral Defects in a Canine Model*

Breinan, Howard A.; Minas, Tom; Hsu, Hu‐Ping; Nehrer, Stefan; Sledge, Clement B.; Spector, Myron

doi:10.2106/00004623-199710000-00001

Cited by 310 publications

(189 citation statements)

References 4 publications

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“…A quantitative histomorphometric analysis [7,33] of specific tissue types was used to evaluate the tissue filling the defects. A recent study evaluated the inter-observer error associated with this quantitative histological method [6].…”

Section: H I S T O T I~o R~~l I O~i I E R~~~mentioning

confidence: 99%

“…In an attempt to prevent or reduce the rate of the progression of widespread degradation of joint cartilage, numerous treatments have been studied as methods for enhancing the repair of focal cartilage defects [26]. There are two basic approaches to cartilage tissue engineering that have been proposed: (1) implantation of cells alone [5][6][7][8][9] or scaffolds alone [5], or in combination as a cell-seeded scaffold [5,10.15,28], to promote regeneration in vivo; or (2) in vitro formation of cartilaginous tissue for subsequent implantation [ 12-1 4,321.…”

Section: Introductionmentioning

confidence: 99%

“…The objective was to evaluate the healing of cartilage defects implanted with autologous chondrocyte-seeded type I1 collagen scaffolds that had been cultured in vitro for four wceks prior to implantation. This study employed the canine model previously reported [6,7,28,33]. Prior work with this model has C.R.…”

Section: Introductionmentioning

confidence: 99%

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Effects of a cultured autologous chondrocyte‐seeded type II collagen scaffold on the healing of a chondral defect in a canine model

Lee

Grodzinsky

Hsu

et al. 2003

Journal Orthopaedic Research

186

110

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Using a previously established canine model for repair of articular cartilage defects, this study evaluated the 15-week healing of chondral defects (i.e., to the tidemark) implanted with an autologous articular chondrocyte-seeded type I1 collagen scaffold that had been cultured in vitro for four weeks prior to implantation. The amount and composition of the reparative tissue were compared to results from our prior studies using the same animal model in which the following groups were analyzed: defects implanted with autologous chondrocyte-seeded collagen scaffolds that had been cultured in vitro for approximately 12 h prior to implantation, defects implanted with autologous chondrocytes alone, and untreated defects. Chondrocytes, isolated from articular cartilage harvested from the left knee joint of six adult canines, were expanded in number in monolayer for three weeks, seeded into porous type I1 collagen scaffolds. cultured for an additional four weeks in vitro and then implanted into chondral defects in the trochlear groove of the right knee joints. The percentages of specific tissue types filling the defects were evaluated histomorphoinetrically and certain mechanical properties of the repair tissue were determined. The reparative tissue filled 88 f 6% (mean * SEM; range 70-100%) of the cross-sectional area of the original defect. with hyaline cartilage accounting for 42 f 10%) (range 7-67'%)) of defect area. These values were greater than thosc reported previously for untreated defects and defects implanted with a type I1 collagen scaffold seeded with autologous chondrocytes within 12 h prior to implantation. Most striking, was the decreased amount of fibrous tissue filling the defects in the current study, 5 & 5%) (range 0-26%) as compared to previous treatments. Despite this improvement, indentation testing of the repair tissue formed in this study revealed that the compressive stiffness of the repair tissue was well below (20-fold lower stiffness) that of native articular cartilage.

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Section: H I S T O T I~o R~~l I O~i I E R~~~mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of a cultured autologous chondrocyte‐seeded type II collagen scaffold on the healing of a chondral defect in a canine model

Lee

Grodzinsky

Hsu

et al. 2003

Journal Orthopaedic Research

186

110

View full text Add to dashboard Cite

show abstract

“…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. One such approach, autologous chondrocyte transplantation, has shown promising results in early clinical studies (7)(8)(9)(10), but findings of recent randomized, controlled trials suggest little difference in the efficacy of this procedure compared with the procedure of inducing microfracture of the subchondral bone (11). Furthermore, autologous chondrocyte transplantation has been associated with significant donor-site morbidity and the initiation of osteoarthritic changes in the joint due simply to harvest of the donor cartilage (12), indicating the need for alternative cell sources for the tissue-engineered repair of cartilage.…”

mentioning

confidence: 99%

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

Estes

Guilak

2006

Arthritis & Rheumatism

269

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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“…[3][4][5] In this model, surgically applied damage to the articular cartilage surface of the weight-bearing areas of only the femoral condyles, not damaging the subchondral bone and not causing joint instability, in analogy to models using cartilage defects as a trigger for osteoarthritis, 6,7 is the trigger for joint damage. To strengthen this trigger for development of OA, loading of the affected joint is intensified by intermittently and temporarily fixing the contralateral control limb to the trunk.…”

mentioning

confidence: 99%

Does loading influence the severity of cartilage degeneration in the canine Groove‐model of OA?

Vos

Interma

El³

et al. 2009

Journal Orthopaedic Research

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Many animal models are used to study osteoarthritis (OA). In these models the role of joint loading in the development of OA is not fully understood. We studied the effect of loading on the development of OA in the canine Groove-model. In ten female beagle dogs OA was induced in one knee according to the Groove-model. The animals were divided in groups with and without forced-loading. Forced-loading was achieved by fixing the contra-lateral limb to the trunk 3 times a week for 4 hours. After 20 weeks joint tissues of all dogs were evaluated. Subjective evaluation revealed less movement with more loading in the forced-loading-group compared to the group without forced-loading. In both groups induction of OA resulted in macroscopical and microscopical OA changes as well as alterations in cartilage metabolism characteristics for OA. Although differences were small, for some parameters they were statistically significant for the forced-loading-group. There were no differences between the contra-lateral healthy joints of both groups. The present study demonstrates that in the Groove-model intensified loading is not a prerequisite for the development of OA, although it adds to some extent to the severity of the OA. ß

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Effect of Cultured Autologous Chondrocytes on Repair of Chondral Defects in a Canine Model*

Cited by 310 publications

References 4 publications

Effects of a cultured autologous chondrocyte‐seeded type II collagen scaffold on the healing of a chondral defect in a canine model

Effects of a cultured autologous chondrocyte‐seeded type II collagen scaffold on the healing of a chondral defect in a canine model

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

Does loading influence the severity of cartilage degeneration in the canine Groove‐model of OA?

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