The role of cell density in the survival of cultured cerebellar granule neurons

The dependence for survival of cerebellar granule neurons on the cell density was examined both experimentally and theoretically. The results of batch experiments revealed that the cell survival index (CSI) was inappreciable, if cell density was below a critical level. If cell density exceeded this critical value, CSI increased with the increase in cell density. In addition, CSI was significantly increased by using a conditioned medium from the dense cultures. This suggests that not only cell density promotes survival of neurons, but also an increased concentration of growth factors produced by neurons has a direct effect on the survival of the neurons. A quantitative model describing the distribution of the growth factor at different cell densities was proposed to investigate the role of cell density in the survival of the neurons. We showed the existence of a critical level for cell density, and good agreement in the improvement of CSI was found between the theoretical prediction and the experimental result. Finally, the average concentration of growth factor necessary for cell survival based on our model was in a reasonable range compared to the practice of the addition of neurotrophic factors to the medium of cultured cerebellar granule neurons. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res, 52, 748–753, 2000.