IDENTIFICATION OF GAS6 AS A GROWTH-FACTOR FOR HUMAN SCHWANN-CELLS

Schwann cells are one of the principal components of the peripheral ne rvous system. They play a crucial role in nerve regeneration and can b e used clinically in the repair of injured nerves. We have established serum-free, defined culture conditions that rapidly expand adult huma n Schwann cells without fibroblast growth. We find that Gas6, a ligand for the Axl and Rse/Tyro3 receptor protein tyrosine kinase family, st imulates human Schwann cell growth, increasing both cell number and th ymidine incorporation. Gas6 has synergistic effects with the other kno wn human Schwann cell mitogens, heregulin/glial growth factor and fors kolin. Addition of Gas6 causes phosphorylation of Art and Rse/Tyro3 si multaneously and results in ERK-2 activation. A combination of Gas6 wi th heregulin and forskolin, on a defined background, supports maximal Schwann cell proliferation, while preserving the typical Schwann cell morphology and expression of the Schwann cell markers S-100, glial fib rillary acidic protein, and low-affinity nerve growth factor receptor. Gas6 mRNA is present in both spinal motor neurons and large neurons o f the dorsal root ganglia, and neural injury has been reported to upre gulate Rse/Axl in the Schwann cell. This is the first demonstration of a potentially important biological role for the human Gas6/Rse-Axl sy stem.