A comparative study of articular cartilage thickness in the stifle of animal species used in human pre-clinical studies compared to articular cartilage thickness in the human knee

Frisbie, David D.; Cross, M. W.; McIlwraith, C. Wayne

doi:10.1055/s-0038-1632990

Cited by 272 publications

(284 citation statements)

References 18 publications

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“…Due to the relatively thin goat cartilage layer (0.7-1.5 mm (Frisbie et al, 2006)), indentation tests of the whole articular surface would have represented the only feasible option. However, the reliability of these tests would be biased by the osteochondral nature of the defects, since the measured stiffness could not have been decoupled from the subchondral tissue properties.…”

Section: Discussionmentioning

confidence: 99%

Influence of in vitro maturation of engineered cartilage on the outcome of osteochondral repair in a goat model

Miot

Brehm²,

Dickinson³

et al. 2012

eCM

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This study was designed to determine if the maturation stage of engineered cartilage implanted in a goat model of cartilage injury infl uences the repair outcome. Goat engineered cartilage was generated from autologous chondrocytes cultured in hyaluronic acid scaffolds using 2 d, 2 weeks or 6 weeks of pre-culture and implanted above hydroxyapatite/hyaluronic acid sponges into osteochondral defects. Control defects were left untreated or treated with cell-free scaffolds. The quality of repair tissues was assessed 8 weeks or 8 months post implantation by histological staining, modifi ed O'Driscoll scoring and biochemical analyses. Increasing pre-culture time resulted in progressive maturation of the grafts in vitro. After 8 weeks in vivo, the quality of the repair was not improved by any treatment. After 8 months, O'Driscoll histology scores indicated poor cartilage architecture for untreated (29.7 ± 1.6) and cell-free treated groups (24.3 ± 5.8). The histology score was improved when cellular grafts were implanted, with best scores observed for grafts pre-cultured for 2 weeks (16.3 ± 5.8). As compared to shorter pre-culture times, grafts cultured for 6 weeks (histology score: 22.3 ± 6.4) displayed highest type II/I collagen ratios but also inferior architecture of the surface and within the defect, as well as lower integration with native cartilage. Thus, pre-culture of engineered cartilage for 2 weeks achieved a suitable compromise between tissue maturity and structural/integrative properties of the repair tissue. The data demonstrate that the stage of development of engineered cartilage is an important parameter to be considered in designing cartilage repair strategies.

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Section: Discussionmentioning

confidence: 99%

Influence of in vitro maturation of engineered cartilage on the outcome of osteochondral repair in a goat model

Miot

Brehm²,

Dickinson³

et al. 2012

eCM

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“…15,19 As for chondrocyte density, there is an opposite relationship between cartilage thickness and cell density, resulting in a fourfold increase in cell density in canines compared to humans. 19,20 The specific activity of chondrocytes from different species can also be variable.…”

Section: Discussionmentioning

confidence: 99%

“…The cartilage of both femoral condyles was damaged by making approximately 10 diagonal grooves to a depth of maximum 0.5 mm on the weight-bearing area preventing subchondral bone damage. 15 The latter was checked by histology at the end of the experiment. There was no absolute visual control over the procedure, but macroscopic evaluation after termination of the animals showed similar patterns in all knees.…”

Section: Canine Experimentally Induced Joint Degenerationmentioning

confidence: 99%

Cartilage integrity and proteoglycan turnover are comparable in canine experimentally induced and human joint degeneration

et al. 2010

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The value of experimental models of osteoarthritis (OA) largely depends on the ability to translate observations to human OA. Surprisingly, direct comparison of characteristics of human and experimental OA is scarce. In the present study, cartilage integrity and matrix turnover in a canine model of joint degeneration were compared to human clinical OA. In 23 Beagle dogs, joint degeneration was induced in one knee, the contra-lateral knee served as a control. For comparison, human osteoarthritic and healthy knee cartilage were obtained at arthroplasty (n=14) and post-mortem (n=13). Cartilage was analyzed by histology and biochemistry. Values for cartilage integrity and proteoglycan (PG) synthesis showed species specific differences; GAG content of healthy cartilage was 2-fold higher in canine cartilage and PG synthesis even 8-fold. However, the relative decrease in PG content between healthy and OA cartilage was similar for humans and canines (-17% vs. -15%, respectively), as was the histological damage (+7.0 vs. +6.1, respectively) and the increase of PG synthesis (+100% vs. +70%, respectively). Remarkably, the percentage release of total and of newly formed PGs in human and canine controls was similar, as was the increase due to degeneration (+65% vs. +81% and +91% vs. +52%, respectively). Despite differences in control conditions, the observed changes in characteristics of cartilage integrity and matrix turnover are similar in a canine model of joint degeneration and human clinical OA. The canine Groove model shows that its characteristics reflect those of human OA which makes the model appropriate for studying human OA.

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“…[30][31][32][33][34] Using the equine medial femorotibial joint as a model for the medial femoral condyle of the human knee, many aspects of the microfracture technique have been studied. [35][36][37][38][39][40] A finding that was subsequently translated into clinical For optimal results, patients should preferably be younger than 45 years of age, have a body mass index less than 30 and experience symptoms (activity related pain, swelling, locking, and catching) for less than 1 year. The defect should be isolated from other lesions and should be smaller than 4 cm 2 .…”

Section: Microfracturementioning

confidence: 99%

Articular cartilage repair and the evolving role of regenerative medicine

Bos¹

2010

OAS

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Among the growing applications of regenerative medicine, clinical articular cartilage repair has now been used for 2 decades and forms a successful example of translational medicine. Cartilage is characterized by a limited intrinsic repair capacity following injury. Articular cartilage defects cause symptoms, are not spontaneously repaired, and are generally believed to result in early osteoarthritis. Marrow stimulation techniques, osteochondral transplantation, and cell-based therapies, such as autologous chondrocyte implantation (ACI) and use of mesenchymal stem cells (MSCs), are used for tissue regeneration, symptom relief, and prevention of further joint degeneration. The exact incidence of cartilage defects and the natural outcome of joints with these lesions are unclear. Currently available cartilage repair techniques are designed for defect treatment in otherwise healthy joints and limbs, mostly in young adults. The natural history studies presented in this review estimated that the prevalence of cartilage lesions in this patient group ranges from 5% to 11%. The background and results from currently available randomized clinical trials of the three mostly used cartilage repair techniques are outlined in this review. Osteochondral transplantation, marrow stimulation, and ACI show improvement of symptoms with an advantage for cell-based techniques, but only a suggestion that risk for joint degeneration can be reduced. MSCs, characterized by their good proliferative capacity and the potential to differentiate into different mesenchymal lineages, form an attractive alternative cell source for cartilage regeneration. Moreover, MSCs provide a regenerative microenvironment by the secretion of bioactive factors. This trophic activity is believed to limit damage and stimulate intrinsic regenerative responses. Finally, important clinical issues are discussed, including techniques to study the role of implanted cells in tissue regeneration using cell labeling and cell tracking, the improvement of cartilage integration, the use of delayed gadolinium-enhanced magnetic resonance imaging of cartilage for early judgment of joint degeneration/regeneration, and the influence of regulatory rules for therapeutic application development.

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A comparative study of articular cartilage thickness in the stifle of animal species used in human pre-clinical studies compared to articular cartilage thickness in the human knee

Cited by 272 publications

References 18 publications

Influence of in vitro maturation of engineered cartilage on the outcome of osteochondral repair in a goat model

Influence of in vitro maturation of engineered cartilage on the outcome of osteochondral repair in a goat model

Cartilage integrity and proteoglycan turnover are comparable in canine experimentally induced and human joint degeneration

Articular cartilage repair and the evolving role of regenerative medicine

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