Synergistic effects of growth and differentiation factor-5 (GDF-5) and insulin on expanded chondrocytes in a 3-D environment

Appel, Bernhard; Julia, Baumer; Eyrich, Daniela; Sarhan, Hatem A.; Toso, Seema; Englert, Carsten; Skodacek, Daniel; Ratzinger, Sabine; Grässel, Susanne; Goepferich, Achim; Blunk, Torsten

doi:10.1016/j.joca.2009.05.002

Cited by 20 publications

(16 citation statements)

References 49 publications

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“…Indeed, it is current practice to use culture media with a high glucose content (4.5 g/L, corresponding to 25 mM) for cartilage tissue engineering [Hennig et al, 2007;Marsano et al, 2007;Das et al, 2008;Appel et al, 2009]. Furthermore, OA cartilage is being increasingly used as a source of chondroprogenitor cells for cartilage tissue engineering [Agar et al, 2011].…”

Section: Discussionmentioning

confidence: 99%

Role of glucose as a modulator of anabolic and catabolic gene expression in normal and osteoarthritic human chondrocytes

et al. 2011

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Cartilage matrix homeostasis involves a dynamic balance between numerous signals that modulate chondrocyte functions. This study aimed at elucidating the role of the extracellular glucose concentration in modulating anabolic and catabolic gene expression in normal and osteoarthritic (OA) human chondrocytes and its ability to modify the gene expression responses induced by pro-anabolic stimuli, namely Transforming Growth Factor-b (TGF). For this, we analyzed by real time RT-PCR the expression of articular cartilage matrix-specific and nonspecific genes, namely collagen types II and I, respectively. The expression of the matrix metalloproteinases (MMPs)-1 and -13, which plays a major role in cartilage degradation in arthritic conditions, and of their tissue inhibitors (TIMP) was also measured. The results showed that exposure to high glucose (30 mM) increased the mRNA levels of both MMPs in OA chondrocytes, whereas in normal ones only MMP-1 increased. Collagen II mRNA was similarly increased in normal and OA chondrocytes, but the increase lasted longer in the later. Exposure to high glucose for 24 h prevented TGF-induced downregulation of MMP-13 gene expression in normal and OA chondrocytes, while the inhibitory effect of TGF on MMP-1 expression was only partially reduced. Other responses were not significantly modified. In conclusion, exposure of human chondrocytes to high glucose, as occurs in vivo in diabetes mellitus patients and in vitro for the production of engineered cartilage, favors the chondrocyte catabolic program. This may promote articular cartilage degradation, facilitating OA development and/or progression, as well as compromise the quality and consequent in vivo efficacy of tissue engineered cartilage. J. Cell. Biochem. 112: 2813Biochem. 112: -2824Biochem. 112: , 2011. ß 2011 Wiley-Liss, Inc. KEY WORDS: COLLAGEN; GENE EXPRESSION; GLUCOSE; HUMAN CHONDROCYTE; MMP; OSTEOARTHRITIS; TIMPA rticular cartilage is a specialized connective tissue that supports and distributes loads and ensures a near-frictionless motion in joints. These unique properties are due to the structural organization of the main macromolecules that compose the cartilage extracellular matrix, namely collagens and proteoglycans. Chondrocytes, the only cell type present in articular cartilage, are embedded in the extracellular matrix and are responsible for maintaining its homeostasis by ensuring the synthesis and turnover of its components [Martel-Pelletier et al., 2008;Goldring and Marcu, 2009].Cartilage matrix homeostasis involves a dynamic balance between a variety of signals that modulate chondrocyte functions, namely mechanical forces, cytokines and growth factors and cellmatrix interactions, some favoring an anabolic program and others stimulating catabolic responses. Aging and mechanical stress of joints are major risk factors for osteoarthritis (OA), but growing evidence indicates that metabolic factors play an important role in disease development and progression. For instance, a significant positive correlation wa...

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Section: Discussionmentioning

confidence: 99%

Role of glucose as a modulator of anabolic and catabolic gene expression in normal and osteoarthritic human chondrocytes

et al. 2011

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“…The dense ECM, responsible for the mechanical properties of cartilage, bears large loads that frequently exceed body weight many‐fold and, thus, presents a difficult task for regeneration. To an extent, these challenges are tackled by soluble factors that assist in cell expansion (Appel et al ., ; Huey et al ., ) and mechanical stimuli to increase biomechanical properties (Kock et al ., ; Lima et al ., ; Makris et al ., ; Responte et al ., ). In terms of stem cells, the use of various factors, such as dynamic compressive loading, resulted in higher expression of chondrogenic genes and improved the mechanical properties of MSC constructs (Huang et al ., ).…”

Section: Application and Advantages Of Co‐culture In Tissue Engineeringmentioning

confidence: 99%

Advances in tissue engineering through stem cell-based co-culture

Paschos

Brown

Eswaramoorthy

et al. 2014

J Tissue Eng Regen Med

164

125

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Stem cells are the future in tissue engineering and regeneration. In a co-culture, stem cells not only provide a target cell source with multipotent differentiation capacity, but can also act as assisting cells that promote tissue homeostasis, metabolism, growth and repair. Their incorporation into coculture systems seems to be important in the creation of complex tissues or organs. In this review, critical aspects of stem cell use in co-culture systems are discussed. Direct and indirect co-culture methodologies used in tissue engineering are described, along with various characteristics of cellular interactions in these systems. Direct cell-cell contact, cell-extracellular matrix interaction and signalling via soluble factors are presented. The advantages of stem cell co-culture strategies and their applications in tissue engineering and regenerative medicine are portrayed through specific examples for several tissues, including orthopaedic soft tissues, bone, heart, vasculature, lung, kidney, liver and nerve. A concise review of the progress and the lessons learned are provided, with a focus on recent developments and their implications. It is hoped that knowledge developed from one tissue can be translated to other tissues. Finally, we address challenges in tissue engineering and regenerative medicine that can potentially be overcome via employing strategies for stem cell co-culture use.

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“…Among the TGF-β superfamily, the most heavily investigated growth factors for cartilage repair include prototypic members TGF-β1, 2, and 3 and bone morphogenetic proteins (BMP) 2, 4, and 7. Growth differentiation factors (GDFs), particularly GDF-5, have shown chondrogenic potential in vitro , but their ability to promote in vivo cartilage repair has yet to be evaluated [18–21]. …”

Section: Cartilage Regenerative Factorsmentioning

confidence: 99%

Strategies for controlled delivery of biologics for cartilage repair

Lam

Kasper

et al. 2015

Advanced Drug Delivery Reviews

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The delivery of biologics is an important component in the treatment of osteoarthritis and the functional restoration of articular cartilage. Numerous factors have been implicated in the cartilage repair process, but the uncontrolled delivery of these factors may not only reduce their full reparative potential and can also cause unwanted morphological effects. It is therefore imperative to consider the type of biologic to be delivered, the method of delivery, and the temporal as well as spatial presentation of the biologic to achieve the desired effect in cartilage repair. Additionally, the delivery of a single factor may not be sufficient in guiding neo-tissue formation, motivating recent research towards the delivery of multiple factors. This review will discuss the roles of various biologics involved in cartilage repair and the different methods of delivery for appropriate healing responses. A number of spatiotemporal strategies will then be emphasized for the controlled delivery of single and multiple bioactive factors in both in vitro and in vivo cartilage tissue engineering applications.

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Synergistic effects of growth and differentiation factor-5 (GDF-5) and insulin on expanded chondrocytes in a 3-D environment

Abstract: In combination with insulin, GDF-5 appears to enable the redifferentiation of expanded chondrocytes and the concurrent generation of cartilaginous constructs. The demonstration of these synergistic effects also for adult human chondrocytes supports the clinical relevance of the findings.

Cited by 20 publications

References 49 publications

Role of glucose as a modulator of anabolic and catabolic gene expression in normal and osteoarthritic human chondrocytes

Role of glucose as a modulator of anabolic and catabolic gene expression in normal and osteoarthritic human chondrocytes

Advances in tissue engineering through stem cell-based co-culture

Strategies for controlled delivery of biologics for cartilage repair

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