Influence of chondrocytes differentiation stage on the capacity to generate cartilaginous tissue in vitro

Abstract

Cartilage lesions resulting from trauma or degenerative diseases are one of the major factors leading to joint disease and disability. Articular cartilage being an avascular tissue has limited capacity for self repair. To overcome these limitations, tissue engineering techniques have emerged as an innovative field of research with the potential to recreate three dimensional cartilaginous tissues. Such approach generally rely on the expansion of a limited population of chondrocytes derived from a small cartilage biopsy, intrinsically associated with cellular de-differentiation (108), and on the ability of the expanded cells to efficiently and reproducibly re-differentiate and generate cartilaginous tissue. The objective of my research was to study different clinically relevant aspects of the biology of human articular chondrocytes, related to different phases in the process of engineering of a functional cartilage tissue (Figure 4). In particular, my thesis was aimed at determining: - whether the supplementation of growth factors enhancing chondrocyte proliferation and re-differentiation capacity allows a reproducible and efficient clinical-scale expansion of human articular chondrocytes (HAC) starting from variable initial seeding densities and using low percentages of human serum (Study 1; Francioli et al., Tissue Eng (2007)); - whether the quality of cartilaginous tissues generated by HAC on three-dimensional biomimetic scaffolds can be enhanced by direct expansion on the scaffold, as compared to standard growth on plastic, or by increasing cell seeding density (Study 2; Francioli et al., Tissue Eng (submitted)); - how the extent of maturation of HAC-based cartilaginous tissues modulates the profile of chemokine production and the inflammatory/catabolic response to IL-1β (Study 3; Francioli et al., Clin Orthop Relat Res (in preparation for submission)).