ADULT HUMAN CHONDROCYTES CULTURED IN ALGINATE FORM A MATRIX SIMILAR TO NATIVE HUMAN ARTICULAR-CARTILAGE

The matrix formed by adult human chondrocytes in alginate beads is com posed of two compartments: a thin rim of cell-associated matrix that c orresponds to the pericellular and territorial matrix of articular car tilage and a more abundant further-removed matrix, the equivalent of t he interterritorial matrix in the tissue. On day 30 of culture, the re lative and absolute volumes occupied by the cells and each of the two matrix compartments in the beads were nearly identical to those in nat ive articular cartilage. Furthermore, the concentration of aggrecan in the cell-associated matrix was similar to that in adult human articul ar cartilage and was similar to 40-fold higher than in the further rem oved matrix compartment. Fluorescence-activated cell sorting revealed that the cell-associated matrix was built on the cell membrane in part via interactions between hyaluronic acid and CD44-like receptors. App roximately 25% of the aggrecan molecules synthesized by the chondrocyt es during a 4-h pulse in the presence of [S-35]sulfate on day 9 of cul ture were retained in the cell-associated matrix where they turned ove r with a half-life (t(1/2)) = 29 days. Most [S-35]aggrecan molecules r eached the further removed matrix compartment where they turned over m uch more slowly (t(1/2) > 100 days). These results add support to the contention that aggrecan molecules residing in the pericellular and te rritorial areas of the adult human articular cartilage matrix are more susceptible to degradation by proteolytic enzymes synthesized by the chondrocytes than those that inhabit the interterritorial areas furthe r removed from the cells.