Differentiation of Human and Murine Chondrogenic Cells Encapsulated in Ultra-High Viscosity Alginate

Abstract

Transplantation of autologous chondrocytes cultured and expanded under in vitro conditions has yielded good to excellent long-term results in 92% of circumscript femoral cartilage lesions (see chapter 1) [22]. A major problem of chondrocyte expansion is the phenomenon of de-differentiation after multiple cell passages [21]. When cultured in monolayers, chondrocytes change their appearance to a fibroblast-like morphology and switch from production of hyaline cartilage-specific collagen type II (and chondroitin-6-sulfate) to synthesis of collagen type I [6, 33]. Re-differentiation and formation of hyaline components can be achieved by encapsulation of the cells in a three-dimensional matrix [15, 20]. Alginate has been extensively employed for in vitro cultures and in animal studies for articular cartilage repair [11, 19, 20, 35]. However, as outlined in Zimmermann et al. (chapter 9, this issue), commercial alginates provoke foreign body reactions, especially when implanted in rats exhibiting an elevated macrophage system. Immunoreactive alginates will not receive medical approval because they do not meet the demands of the guidelines of the American Society for Testing and Materials (ASTM) and GMP/ISO 9000 [9]. Use of commercial alginates for in vitro and animal studies is also not recommendable because the contaminants might affect the metabolic, secretory and/or growth properties of the entrapped cells in an unpredictable way.

We are very grateful to M. Behringer, P. Geßner and A. Steinbach for skilful technical assistance. This work was supported by grants fro the Landesgewerbeanstalt (High-Tech-Offensive des Freistaates Bayern), from the Deutsche Forschungsgemeinschaft (Zi 99/16-1) and BMBF (VDI 16SV1329) to U.Z., and by a grant from BMBF (VDI 16SV1366/0) to H. Z.