Adhesive Force of Chondrocytes to Cartilage

Lee, Myung Chul; Sung, K.L. Paul; Kurtis, Melissa S.; Akeson, Wayne H.; Sah, Robert L.

doi:10.1097/00003086-200001000-00029

Cited by 64 publications

(57 citation statements)

References 45 publications

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“…3A), and adult cartilage with trypsin 131, on integration of cartilage explants, does not preclude the possibility that such treatments could still enhance repair in vivo through other mechanisms [15]. Such treatments facilitate cell adhesion, possibly through a mechanism dependent on aggrecan removal [20,22], and could enhance repair by facilitating attachment of extrinsic repair cells.…”

Section: Discussionmentioning

confidence: 99%

Development‐associated differences in integrative cartilage repair: Roles of biosynthesis and matrix

Giurea

DiMicco

Akeson

et al. 2002

Journal Orthopaedic Research

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A recurring problem in tissue transplantation therapies for articular cartilage defects is the lack of integration between the implant and the host cartilage. Previous studies have shown that in vitro integration between explants of calf cartilage is markedly higher than that between fetal cartilage, despite similarly high levels of deposition of newly synthesized collagen. The aim of this study was to determine if cellular biosynthesis and extracellular matrix each contribute to these development-associated differences in integrative repair in vitro. The approach taken was to examine integration between specific combinations of cartilage explants that were apposed for two weeks. The cartilage matrix showed different propensities for repair, as integration of calf live cartilage to calf devitalized cartilage was greater than that of calf live cartilage to fetal devitalized cartilage. An inhibiting factor appeared to be present in fetal cartilage matrix since guanidine treatment of fetal devitalized cartilage was able to enhance its integration. The difference between integration to living cartilage and integration to devitalized cartilage, for calf and fetal tissue, indicated that the biosynthetic contribution to integration by calf cartilage was greater than the biosynthetic contribution by fetal cartilage. Thus, the increasing level of integration between fetal and fetal cartilage, fetal and calf cartilage, and calf and calf cartilage appeared to reflect both biosynthetic and matrix differences. Therapeutic strategies to enhance integration to cartilage may thus target both the extracellular components and the cellular biosynthetic activities of implants and host cartilage.

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Section: Discussionmentioning

confidence: 99%

Development‐associated differences in integrative cartilage repair: Roles of biosynthesis and matrix

Giurea

DiMicco

Akeson

et al. 2002

Journal Orthopaedic Research

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“…Initial time course experiments using published concentrations and incubation times for chondroitinase ABC digestion (Hunziker and Kapfinger, 1998;Hunziker and Rosenberg, 1996;Lee et al, 2000), lU/ml chondroitinase ABC for periods between 0-1 hr, demonstrated no detectable digestion of the GAG content of the cartilage beyond the wound surface (data not shown). The described results therefore used a 1 hour incubation time and lU/ml concentration of enzyme as the minimum conditions.…”

Section: The Effect O F Concentration and Incubation Time O F Chondromentioning

confidence: 96%

“…Recent research suggests that removal of the proteoglycans at the wound edges by enzymatic treatment may act to improve adhesion of transplanted chondrocytes and integration (Giurea et al, 2002;Hunziker and Rosenberg, 1996;van de Breevaart Bravenboer et al, 2004). Specifically a number of studies have used the enzyme chondroitinase ABC to pre-treat the wound edge (Hunziker and Kapfinger, 1998;Lee et al, 2000). This enzyme, at pH 8.0, specifically targets the CS GAG chains attached to the aggrecan core protein as well as the SLRPs (Yamagata et al, 1968).…”

Section: Adhesion and Integrationmentioning

confidence: 99%

“…Studies to date have only allowed limited incubation of cartilage with chondroitinase ABC in order to digest sufficient proteoglycan for enhancing chondrocyte adherence to the wound surface (Hunziker and Kapfmger, 1998;Hunziker and Rosenberg, 1996;Lee et al, 2000). In this chapter, I investigated whether prolonged digestion with this enzyme will allow not only adherence but also migration of the transplanted cells.…”

Section: Introductionmentioning

confidence: 99%

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Novel strategies for enhancing tissue integration in cartilage repair

Davies

Caterson

Duance

2004

Int J Experimental Path

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Introduction Articular cartilage is unable to initiate a spontaneous repair response when injured due to its avascular and aneural properties. Within adult cartilage, chondrocytes are entrapped within an extensive extracellular matrix and are unable to migrate to sights of injury to regulate tissue repair. Injury to this tissue therefore inevitably leads to degeneration of the cartilage and the development of degenerative diseases such as osteoarthritis. The surgical technique of autologous chondrocyte transplantation (ACT) was developed for the treatment of full‐thickness cartilage defects (Brittberg et al. 1994). Implantation of chondrocytes into the defect site repairs the injury site with a mixture of fibrocartilaginous and hyaline‐like tissue that poorly integrates with the existing cartilage and frequently degenerates with time. In this current study, we have developed an in vitro model to investigate methods for enhancing this integration and the development of a more biomechanically stable repair tissue. Materials and methods Bovine articular cartilage explants from the metacarpalphalangeal joint were experimentally injured using a stainless steel trephine and cultured for a period of 28 days. Autologous chondrocytes in an agarose suspension were injected into the interface region at the injury site. Media was collected and analysed for proteoglycan and collagen content using the DMMB and hydroxyproline assays, respectively. Matrix metalloproteinase (MMP) expression was also analysed using zymography and an adapted collagen fibril assay. Results Morphological analyses indicate attempts at repair and integration within both control and experimental treatment groups, although the presence of autologous chondrocytes appeared to amplify this repair response. Although not statistically significant, considerable differences in proteoglycan release between injured explants and the intact control group were seen. Collagen release into the media was only seen at day 28 within experimental cultures. An up‐regulation of MMP‐2 and MMP‐9 was seen within the experimental cultures compared to the controls. Preliminary data also suggest up‐regulation of collagenases in the experimental group when compared to controls. Discussion As seen with clinical ACT treatment, the presence of autologous chondrocytes appears to enhance repair and integration attempts; however, morphologically, this repair tissue appears to be fibrocartilaginous. Further analysis will establish whether the repair tissue is true hyaline cartilage and monitor the synthesis and turnover of macromolecules within the established culture system.

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“…112,116,117 Enzymatic removal of proteoglycans or glycosaminoglycan (GAG) chains from the cartilage lesion edges by using chondroitinase ABC, trypsin, or hyaluronidase has been shown to improve the initial adhesion of transplanted cells 118 or cartilage-to-cartilage wound edges. 119,120 Components of the synovial fluid may have an inhibitory effect on integrative cartilage repair. Proteoglycan 4 (PRG4 or lubricin), present in the synovial fluid, normally acting as a lubricant of articular surfaces was shown to strongly reduce cartilage integration.…”

Section: Integrative Cartilage Repairmentioning

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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Adhesive Force of Chondrocytes to Cartilage

Cited by 64 publications

References 45 publications

Development‐associated differences in integrative cartilage repair: Roles of biosynthesis and matrix

Development‐associated differences in integrative cartilage repair: Roles of biosynthesis and matrix

Novel strategies for enhancing tissue integration in cartilage repair

Articular cartilage repair and the evolving role of regenerative medicine

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