Autologous Chondrocytes Used for Articular Cartilage Repair

Brittberg, Mats; Tallheden, Tommi; Sjögren-Jansson, B; Lindahl, Anders; Peterson, Lars

doi:10.1097/00003086-200110001-00031

Cited by 231 publications

(123 citation statements)

References 26 publications

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“…Prevention of degeneration and matrix re-synthesis could be achieved by replenishment of the NP cell population through autologous cell implantation. Autologous chondrocyte implantation has had some success at repairing focal cartilage defects in patients (Brittberg et al, 1994;Brittberg et al, 2001). Autologous stem cell implantation for IVD repair has shown some clinical promise (Orozco et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis in continuous expansion of bovine and human primary nucleus pulposus cells for tissue repair applications

Rosenzweig¹,

Gravel²,

Bisson³

et al. 2017

eCM

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Autologous NP cell implantation is a potential therapeutic avenue for intervertebral disc (IVD) degeneration. However, monolayer expansion of cells isolated from surgical samples may negatively impact matrix production by way of dedifferentiation. Previously, we have used a continuous expansion culture system to successfully preserve a chondrocyte phenotype. In this work, we hypothesised that continuous expansion culture could also preserve nucleus pulposus (NP) phenotype. We confirmed that serial passaging drove NP dedifferentiation by significantly decreasing collagen type II, aggrecan and chondroadherin (CHAD) gene expression, compared to freshly isolated cells. Proliferation, gene expression profile and matrix production in both culture conditions were compared using primary bovine NP cells. Both standard culture and continuous culture produced clinically relevant cell populations. However, continuous culture cells maintained significantly higher collagen type II, aggrecan and CHAD transcript expression levels. Also, continuous expansion cells generated greater amounts of proteoglycan, collagen type II and aggrecan protein deposition in pellet cultures. To our surprise, continuous expansion of human intervertebral disc cells -isolated from acute herniation tissue -produced less collagen type II, aggrecan and CHAD genes and proteins, compared to standard culture. Also, continuous culture of cells isolated from young non-degenerate tissue did not preserve gene and protein expression, compared to standard culture. These data indicated that primary bovine and human NP cells responded differently to continuous culture, where the positive effects observed for bovine cells did not translate to human cells. Therefore, caution must be exercised when choosing animal models and cell sources for pre-clinical studies.

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Section: Introductionmentioning

confidence: 99%

Comparative analysis in continuous expansion of bovine and human primary nucleus pulposus cells for tissue repair applications

Rosenzweig¹,

Gravel²,

Bisson³

et al. 2017

eCM

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“…These culture-expanded cells are then seeded onto a suitable 3-dimensional scaffold, induced to develop into a tissue-like structure in vitro, [8][9][10][11][12] and/or are implanted in vivo into an orthotopic site to repair or replace a damaged tissue. 13 Ultimately, the phenotype of a cell-based tissue-engineered construct depends on a number of factors, such as the composition, shape, size, porosity, and biodegradability of the scaffold, as well as the type, density, and spatial distribution of the cells within the construct. 14 For example, the cellularity of the engineered construct depends on the number of cells initially introduced into the construct, on the retention of these cells during the first few hours to days, until cell-cell and cell-scaffold interactions have been established, and on the mitotic activity of the cells incorporated into the construct.…”

Section: Introductionmentioning

confidence: 99%

A Rapid Seeding Technique for the Assembly of Large Cell/Scaffold Composite Constructs

Solchaga¹,

Tognana²,

Penick³

et al. 2006

Tissue Engineering

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These studies address critical technical issues involved in creating human mesenchymal stem cell (hMSC)/scaffold implants for cartilage repair. These issues include obtaining a high cell density and uniform spatial cell distribution within the scaffold, factors that are critical in the initiation and homogeneity of chondrogenic differentiation. For any given scaffold, the initial seeding influences cell density, retention, and spatial distribution within the scaffold, which eventually will affect the function of the construct. Here, we discuss the development of a vacuum-aided seeding technique for HYAFF ® -11 sponges which we compared to passive infiltration. Our results show that, under the conditions tested, hMSCs were quantitatively and homogeneously loaded into the scaffolds with 90+% retention rates after 24 h in perfusion culture with no negative effect on cell viability or chondrogenic potential. The retention rates of the vacuum-seeded constructs were at least 2 times greater than those of passively seeded constructs at 72 h. Histomorphometric analysis revealed that the core of the vacuum-seeded constructs contained 240% more cells than the core of passively infiltrated scaffolds. The vacuum seeding technique is safe, rapid, reproducible, and results in controlled quantitative cell loading, high retention, and uniform distribution.

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“…In the case of autologous chondrocyte implantation (ACI), chondrocytes removed from patients are multiplied in vitro by monolayer culture to reach a minimum density of 10 million cells before they are implanted into the cartilage defect. 2 Although accumulating evidence suggest that the clinical outcome of ACI for cartilage defects is promising and has achieved up to 90% good to excellent functional improvement, [3][4][5] the biology of the chondrocytes, in particular the stability of the chondrocyte phenotype during in vitro propagation, has not been well elucidated.…”

mentioning

confidence: 99%

“…[1][2][3][4][5]20 In this study, the gene expression profiles of normal and OA chondrocytes were compared. Surprisingly, little significant difference was observed between the two groups, suggesting that the in vitro biosynthetic profile of the chondrocyte is influenced more by the culture conditions, than the disease state of the donor cartilage.…”

mentioning

confidence: 99%

Gene expression profiles of human chondrocytes during passaged monolayer cultivation

Lin

Fitzgerald

et al. 2008

Journal Orthopaedic Research

178

149

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Chondrocyte phenotype has been shown to dedifferentiate during passaged monolayer cultivation. Hence, we have investigated the expression profile of 27 chondrocyte-associated genes from both osteoarthritic cartilage tissue and healthy passaged human articular chondrocytes by quantitative real-time PCR. Our results indicate that the gene expression levels of matrix proteins and proteases in chondrocytes from monolayer culture decrease compared with those from cartilage tissue, while monolayer cultured chondrocytes from normal and osteoarthritic cartilage exhibit similar gene expression patterns. However, chondrocytic gene expression profiles were differentially altered at various stages of passage. The expression of the matrix proteins aggrecan, type II collagen, and fibromodulin inversely correlated with increasing passage number, while fibronectin and link protein exhibited a marked increase with passage. The expression of matrix proteinases MMP-3/9/13 and ADAMTS-4/5 decreased with passage, whereas proteinase inhibitors TIMP-2/3 were elevated. The cytokine IL-1 also showed increased expression with monolayer chondrocyte culture, while IGF-1 expression levels were diminished. No significant changes in TGF-b, or the chondrogenic transcription factors Sox-9, c-fos, or c-jun were observed. Our data indicates that cultured chondrocytes undergo dedifferentiation during monolayer culture, although the gene expression level of transcription factors necessary for chondrogenesis remains unchanged. This data may prove important for the future development of more specific and efficacious cultivation techniques for human articular chondrocyte-based therapies. ß

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Autologous Chondrocytes Used for Articular Cartilage Repair

Cited by 231 publications

References 26 publications

Comparative analysis in continuous expansion of bovine and human primary nucleus pulposus cells for tissue repair applications

Comparative analysis in continuous expansion of bovine and human primary nucleus pulposus cells for tissue repair applications

A Rapid Seeding Technique for the Assembly of Large Cell/Scaffold Composite Constructs

Gene expression profiles of human chondrocytes during passaged monolayer cultivation

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