The matrix-forming phenotype of cultured human meniscus cells is enhanced after culture with fibroblast growth factor 2 and is further stimulated by hypoxia

The meniscus is a fibrocartilaginous tissue found within the knee joint; it is responsible for shock absorption, load distribution, joint stability and protection of the articular cartilage [1-3]. Unfortunately, the reparative ability of the meniscus is limited, and injuries to the tissue are often treated by partial or total menisectomy, which is known to be associated with detrimental changes in joint function and high incidence of early osteoarthritis [4,5]. Cell-based tissue engineering strategies have been proposed for the generation of meniscus substitute to aid repair of the tissue [6-10]. Like most musculoskeletal tissues, the biomechanical and functional properties of the meniscus depend on the composition and organization of its extracellular matrix (ECM) [1,11]. The cells that produce and maintain this ECM have been called fibrochondrocytes [12]. Although the predominant morphology of these cells resembles that of the chondrocytes of articular cartilage [1], they produce predominantly type I collagen with smaller amounts of types II, III, V and VI collagens, and small amounts of aggrecan [13]. Isolated primary human meniscus cells show some characteristics similar to those of chondrocytes because during expansion in monolayer culture there is a sharp decrease in the expression of collagen type II and a change to predominantly fibroblast-like morphology [7]. This decline in type II collagen expression is reminiscent of the loss of differentiated phenotype of articular chondrocytes, and the use of these cells for tissue regeneration of meniscus might lead to the production of ECM of inferior biomechanical properties. Several investigators have reported strategies to restore the matrix-forming phenotype of articular chondrocytes. These include culturing chondrocytes at high cell densities to prevent cell flattening [14], in alginate gels [15] to retain the round chondrocytic morphology, in liquid suspension or in the presence of actin-disrupting agents, in t