Abstract
The ability to culture cells from the human nervous system provides new insight into the pathophysiology of neurological diseases and could be crucial to the development of gene replacement therapies and neural transplantation. We report that the proliferation of human Schwann cells isolated from paediatric and adult nerves is sustained in vitro by recombinant glial growth factor. Agents that increase intracellular cyclic cAMP were also mitogenic towards Schwann cells but suppress growth of contaminating fibroblasts. As the lifespan of highly enriched cultures can be extended for up to twelve population doublings, large numbers of cells can be generated from nerve biopsies.
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References
Fawcett, J. W. & Keynes, R. J. Peripheral nerve regeneration. Rev. Neurosci. 13, 43–60 (1990).
Raivich, G. & Kreutzberg, G. W. Peripheral nerve regeneration: Role of growth factors and their receptors. Int. J. dev. Neurosci. 11, 311–324 (1993).
Raff, M. C., Abney, E., Brockes, J. P. & Hornby-Smith, A., Schwann cell growth factors. Cell 15, 813–822 (1978).
Goodearl, A. D. et al. Purification of multiple forms of glial growth factor. J. biol Chem. 268, 18095–18102 (1993).
Marchionni, M. A. et al. Glial growth factors are alternatively spliced erbB2 lig-ands expressed in the nervous system. Nature 362, 312–318 (1993).
Peles, E. & Yarden, Y. Neu and its ligands: From an oncogene to neural factors. Bioessays 15, 815–824 (1993).
Carraway, K. L. & Cantley, L.C. A neu acquaintance for erbB3 and erbB4: A role for receptor heterodimerization in growth signaling. Cell 78, 5–8 (1994).
Salzer, J. L. & Bunge, R. P. Studies of Schwann cell proliferation. I. An analysis in tissue culture of proliferation during development, Wallerian degeneration, and direct injury. J. Cell Biol. 84, 739–752 (1980).
Espinosa, B. & Wharton, W. Effects of cholera toxin and isobutylmethylxanthine on growth of human fibroblasts. Am. J. Physiol 251, C238–246 (1986).
Cohen, J. A., Yachnis, A. T., Aral, M., Davis, J. G. & Scherer, S. S. Expression of the neu proto-oncogene by Schwann cells during peripheral nerve development and Wallerian degeneration. J. Neurosci. Res. 31, 622–634 (1992).
Porter, S., Glaser, L. & Bunge, R. P. Release of autocrine growth factor by primary and immortalized Schwann cells. Proc. natn. Acad. Sci. U.S.A. 84, 7768–7772 (1987).
Muir, D., Varon, S. & Manthorpe, M., Schwann cell proliferation in vitro is under negative autocrine control. J. Cell Biol. 111, 2663–2671 (1990).
Bolin, L. M., Iismaa, T. P. & Shooter, E. M. Isolation of activated adult Schwann cells and a spontaneously immortal Schwann cell clone. J. Neurosci. Res. 33, 231–238 (1992).
Davis, J. B. & Stroobant, P. Platelet-derived growth factors and fibroblast growth factors are mitogens for rat Schwann cells. J. Cell Biol. 110, 1353–1360 (1990).
Askanas, V., Engel, W. K., Dalakas, M. C., Lawrence, J. V. & Carter, L. S. Human Schwann cells in tissue culture: Histochemical and ultrastructural studies. Arch. Neurol. 37, 329–337 (1980).
Moretto, G., Kim, S. U., Shin, D. H., Pleasure, D. E. & Rizzuro, N. Long-term cultures of human adult Schwann cells isolated from autopsy materials. Acta. Neuropath. 64, 15–21 (1984).
Scarpini, E. et al. Cultures of human Schwann cells isolated from fetal nerves. Brain Res. 440, 261–266 (1988).
Kim, S. U., Yong, V. W., Watabe, K. & Shin, D. H. Human fetal Schwann cells in culture: Phenotypic expressions and proliferative capability. J. Neurosci. Res. 22, 50–59 (1989).
Rutkowski, J. L., Tennekoon, G. I. & McGillicuddy, J. E. Selective culture of mi-totically active human Schwann cells from adult sural nerves. Ann. Neurol 31, 580–586 (1992).
Levi, A. D. O., Guenard, V., Aebischer, P. & Bunge, R. P. The functional characteristics of Schwann cells cultured from human peripheral nerve after transplantation into a gap within the rat sciatic nerve. J. Neurosci. 14, 1309–1319 (1994).
Chance, P. F. & Pleasure, D. Charcot-Marie-Tooth syndrome. Arch. Neurol 50, 1180–1184 (1993).
Aicardi, J. The inherited leukodystrophies: A clinical overview. J. Inherit. Metab. Dis. 16, 733–743 (1993).
Gutmann, D. H. New insights into the neurofibromatoses. Curr. Opin. Neurol. 7, 166–171 (1994).
Hughes, R. A. The spectrum of acquired demyelinating polyradiculoneuropathy. Acta Neurol. Belg. 94, 128–132 (1994).
Zager, E. L. & Black, P. M. Neural transplantation. Surg. Neurol. 29, 350–366 (1988).
Bunge, R. P., Kleitman, N., Ard, M. D. & Duncan, I. D. Culture preparations of neuroglial cells useful for studies of myelin repair and axonal regeneration in the central nervous system. Prog. Brain Res. 78, 312–316 (1988).
Fisher, L. J. & Gage, F. H. Grafting in the mammalian central nervous system. Physiol Rev. 73, 583–616 (1993).
Brockes, J. P. Assay and isolation of glial growth factor from the bovine pituitary. Meth. Enzym. 147, 217–225 (1987).
Boyer, P. J. et al. Sources of human Schwann cells and the influence of donor age. Expl Neurol 130, 53–54 (1994).
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Rutkowski, J., Kirk, C., Lerner, M. et al. Purification and expansion of human Schwann cells in vitro. Nat Med 1, 80–83 (1995). https://doi.org/10.1038/nm0195-80
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DOI: https://doi.org/10.1038/nm0195-80
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