Growth factor modulation of injury-reactive ependymal cell proliferation and migration

Abstract

Injury-reactive ependymal cells from regenerating axolotl spinal cord can be maintained in their mesenchymal outgrowth phase in culture (O'Hara et al., 1992). To address the ability of specific growth factors in stimulating or maintaining migration and proliferation, mesenchymal ependymal cell cultures derived from injured axolotl spinal cord at 2 weeks post-lesioning were used to determine the potential effects of epidermal growth factor, platelet-derived growth factor and transforming growth factor-beta 1. In our cultures, medium containing epidermal growth factor alone or in combination with the other growth factors permitted significant migration and proliferation from ependymal explants. Platelet-derived growth factor alone was shown to have a small positive effect on ependymal cell migration and no effect on proliferation. Transforming growth factor-beta 1 alone did not support cell migration and was found to be inhibitory towards cellular proliferation. Lastly, medium containing platelet-derived growth factor and transforming growth factor-beta 1, but not epidermal growth factor, caused ependymal cell explants to break apart and migrate on the dish as cords. Migration and proliferation of injury-reactive ependymal cells was shown to be dependent on epidermal growth factor in vitro. These results suggest that epidermal growth factor may be a critical component in vivo during the initiation of ependymal migration and proliferation following transection of the axolotl spinal cord. The reorganization of cultured ependymal cells in response to the combination of platelet-derived growth factor and transforming growth factor-beta shows that ependymal organization can be modulated by growth factors. This suggests that the progressive changes observed during regeneration may be under the control of growth factors.