Reduced neuronotrophic activity of fibroblasts from individuals with dysautonomia in cultures of newborn mouse sensory ganglion cells.

The neuronotrophic activity of human skin fibroblast cell lines from two normal individuals and 3 individuals with Familial Dysautonomia (FD) was compared in terms of their ability to support neuron survival and neurite regeneration in cultures of newborn mouse sensory neurons. Neuronotrophic activity was assayed by culturing dissociated sensory neurons from newborn mice: (1) on fibroblast 'cell beds' consisting of monolayer cultures of living fibroblasts, (2) with medium that had been conditioned by monolayer fibroblast cultures and (3) with extracts of the cultured fibroblasts. Neurite regeneration was compared by determining the percentage of neurons that had regenerated neurites after 24 or 48 h in culture. Neuron survival was determined by counts at 48 h, 7 days and 14 days after culture initiation. Neurite regeneration and neuron survival was found to be significantly less on FD cell beds or with FD-conditioned medium than in replicate cultures with normal fibroblasts or their conditioned medium. The reduced neuronotrophic activity of FD fibroblasts or conditioned medium was still observed in the presence of antibody sufficient to block the neuronotrophic effects of purified nerve growth factor (NGF). Thus, fibroblasts from individuals with FD exhibit reduced neuronotrophic activity for newborn mouse sensory neurons that appears to be due to factor(s) other than NGF.