Proliferation and differentiation potential of chondrocytes from osteoarthritic patients

Autologous chondrocyte transplantation (ACT) has been shown, in long-term follow-up studies, to be a promising treatment for the repair of isolated cartilage lesions. The method is based on an implantation of in vitro expanded chondrocytes originating from a small cartilage biopsy harvested from a non-weight-bearing area within the joint. In patients with osteoarthritis (OA), there is a need for the resurfacing of large areas, which could potentially be made by using a scaffold in combination with culture-expanded cells. As a first step towards a cell-based therapy for OA, we therefore investigated the expansion and redifferentiation potential in vitro of chondrocytes isolated from patients undergoing total knee replacement. The results demonstrate that OA chondrocytes have a good proliferation potential and are able to redifferentiate in a three-dimensional pellet model. During the redifferentiation, the OA cells expressed increasing amounts of DNA and proteoglycans, and at day 14 the cells from all donors contained type II collagen-rich matrix. The accumulation of proteoglycans was in comparable amounts to those from ACT donors, whereas total collagen was significantly lower in all of the redifferentiated OA chondrocytes. When the OA chondrocytes were loaded into a scaffold based on hyaluronic acid, they bound to the scaffold and produced cartilage-specific matrix proteins. Thus, autologous chondrocytes are a potential source for the biological treatment of OA patients but the limited collagen synthesis of the OA chondrocytes needs to be further explained.

[1]  V. Goldberg,et al.  Hyaluronic acid‐based polymers as cell carriers for tissue‐engineered repair of bone and cartilage , 1999, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[2]  C. Ohlsson,et al.  Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. , 1994, The New England journal of medicine.

[3]  Paola Brun,et al.  Tissue-specific gene expression in chondrocytes grown on three-dimensional hyaluronic acid scaffolds. , 2003, Biomaterials.

[4]  S. Bulstra,et al.  Metabolic characteristics of in vitro cultured human chondrocytes in relation to the histopathologic grade of osteoarthritis. , 1989, Clinical orthopaedics and related research.

[5]  E. Kastenbauer,et al.  Cartilage tissue engineering with novel nonwoven structured biomaterial based on hyaluronic acid benzyl ester. , 1998, Journal of biomedical materials research.

[6]  A I Caplan,et al.  In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. , 1998, Experimental cell research.

[7]  R. Teshima,et al.  Comparative rates of proteoglycan synthesis and size of proteoglycans in normal and osteoarthritic chondrocytes. , 1983, Arthritis and rheumatism.

[8]  M Moras,et al.  Biocompatibility and biodegradation of different hyaluronan derivatives (Hyaff) implanted in rats. , 1993, Biomaterials.

[9]  F. Young Biochemistry , 1955, The Indian Medical Gazette.

[10]  S. Cannon,et al.  The use of chondrogide membrane in autologous chondrocyte implantation. , 2004, The Knee.

[11]  J. Vacanti,et al.  Tissue-engineered growth of cartilage: the effect of varying the concentration of chondrocytes seeded onto synthetic polymer matrices. , 1994, International journal of oral and maxillofacial surgery.

[12]  R Langer,et al.  Stabilized polyglycolic acid fibre-based tubes for tissue engineering. , 1996, Biomaterials.

[13]  C. Brantsing,et al.  Human Serum for Culture of Articular Chondrocytes , 2005, Cell transplantation.

[14]  Maurilio Marcacci,et al.  Hyaluronan-based scaffolds (Hyalograft C) in the treatment of knee cartilage defects: preliminary clinical findings. , 2003, Novartis Foundation symposium.

[15]  R. Cancedda,et al.  Response of young, aged and osteoarthritic human articular chondrocytes to inflammatory cytokines: molecular and cellular aspects. , 2002, Matrix biology : journal of the International Society for Matrix Biology.

[16]  H. Dorfman,et al.  Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. , 1971, The Journal of bone and joint surgery. American volume.

[17]  F. Grassi,et al.  Autologous Chondrocyte Implantation Using a Bilayer Collagen Membrane: A Preliminary Report , 2003, Journal of orthopaedic surgery.

[18]  F. Luyten,et al.  Expanded phenotypically stable chondrocytes persist in the repair tissue and contribute to cartilage matrix formation and structural integration in a goat model of autologous chondrocyte implantation , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[19]  V Vécsei,et al.  Dedifferentiation-associated changes in morphology and gene expression in primary human articular chondrocytes in cell culture. , 2002, Osteoarthritis and cartilage.

[20]  B. Swoboda,et al.  Expression of early and late differentiation markers (proliferating cell nuclear antigen, syndecan-3, annexin VI, and alkaline phosphatase) by human osteoarthritic chondrocytes. , 2001, The American journal of pathology.

[21]  M. A. R. Freeman,et al.  Adult Articular Cartilage , 1973 .

[22]  Thomas Aigner,et al.  Articular cartilage and changes in Arthritis: Cell biology of osteoarthritis , 2001, Arthritis Research & Therapy.

[23]  H J Mankin,et al.  Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. , 1970, The Journal of bone and joint surgery. American volume.

[24]  E B Hunziker,et al.  Quantitative structural organization of normal adult human articular cartilage. , 2002, Osteoarthritis and cartilage.

[25]  A. Lindahl,et al.  Phenotypic Plasticity of Human Articular Chondrocytes , 2003, The Journal of bone and joint surgery. American volume.

[26]  B. Obradovic,et al.  Integration of engineered cartilage , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[27]  D. Wendt,et al.  Oscillating perfusion of cell suspensions through three‐dimensional scaffolds enhances cell seeding efficiency and uniformity , 2003, Biotechnology and bioengineering.

[28]  I. Martin,et al.  Quantitative analysis of gene expression in human articular cartilage from normal and osteoarthritic joints. , 2001, Osteoarthritis and cartilage.

[29]  A. Lindahl,et al.  Gene expression during redifferentiation of human articular chondrocytes. , 2004, Osteoarthritis and cartilage.

[30]  P. Mainil-Varlet,et al.  Immunophenotypic analysis of human articular chondrocytes: Changes in surface markers associated with cell expansion in monolayer culture , 2005, Journal of cellular physiology.

[31]  F. Luyten,et al.  Molecular markers predictive of the capacity of expanded human articular chondrocytes to form stable cartilage in vivo. , 2001, Arthritis and rheumatism.

[32]  M. Heberer,et al.  Specific growth factors during the expansion and redifferentiation of adult human articular chondrocytes enhance chondrogenesis and cartilaginous tissue formation in vitro , 2001, Journal of cellular biochemistry.