KAGAKU KOGAKU RONBUNSHU, Vol.30, No.4, 515-521, 2004
A three-dimensional growth model for chondrocytes embedded in collagen gel
A three-dimensional growth model with cell placement was proposed to express the growth manner of rabbit chondrocytes embedded in collagen gel. This model allows the description of a growth profile consisting of lag and exponential growth phases as well as a stationary phase caused by spatial restriction of cell division (spatial contact inhibition), by considering that the gel matrix is compartmentalized into a set of unit cubes equivalent to the average cell volume, and that the spatial distribution of dissolved oxygen is a limiting factor for growth rate (generation time) of the respective cells. In the cultures conducted at initial cell densities of X-0 = 1.1 X 10(5) and 6.8 X 10(5) cells/cm(3)-gel, the calculated values of cell density based on the model were in fair agreement with the experimental data. Further model analysis was conducted to evaluate the contributions of dissolved oxygen concentration and local cell density to cell division, and it was demonstrated that the effect of spatial contact inhibition become of significance at low cell density in the case of X-0 = 1.1 X 10(5) cells/cm(3)-gel as compared with X-0 = 6.8 X 10(5) cells/cm(3)-gel. It was also found that relatively small cell aggregates were interspersed inside the gel matrix when X-0 = 6.8 X 10(5) cells/cm(3)-gel, whereas the chondrocytes formed larger cell aggregates in the case of X-0 = 1.1 X 10(5) cells/cm(3)-gel. The proposed model can be a useful tool to estimate the overall cell propagation and spatial cell distribution in the collagen-gel embedded culture of chondrocytes.