Mammalian chondrocytes expanded in the presence of fibroblast growth factor 2 maintain the ability to differentiate and regenerate three-dimensional cartilaginous tissue

The differentiated phenotype of chondrocytes from hyaline cartilage is grad ually lost during expansion in monolayers. Chondrocytes can reexpress their differentiated phenotype by transfer into an environment that prevents cel l flattening, but serially passaged cells never completely recover their ch ondrogenic potential. We report that chondrocytes expanded (up to 2000-fold ) in the presence of fibroblast growth factor 2 (FGF-2) dedifferentiated, b ut fully maintained their potential for redifferentiation in response to en vironmental changes. After seeding onto three-dimensional polymer scaffolds , chondrocytes expanded in the presence of FGF-2 formed cartilaginous tissu e that was histologically and biochemically comparable to that obtained usi ng primary chondrocytes, in contrast to chondrocytes expanded to the same d egree but in the absence of FGF-2. The presence of FGF-2 inhibited the form ation of thick F-actin structures, which otherwise formed during monolayer expansion, were maintained during tissue cultivation, and were associated w ith reduced ability of chondrocytes to reexpress their differentiated pheno type. This study provides evidence that FGF-2 maintains the chondrogenic po tential during chondrocyte expansion in monolayers, possibly due to changes in the architecture of F-actin elements and allows more efficient utilizat ion of harvested tissue for cartilage tissue engineering, (C) 1999 Academic Press.