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. 1994 Nov 22;91(24):11616–11620. doi: 10.1073/pnas.91.24.11616

Transplantation of an oligodendrocyte cell line leading to extensive myelination.

U Tontsch 1, D R Archer 1, M Dubois-Dalcq 1, I D Duncan 1
PMCID: PMC45282  PMID: 7972113

Abstract

Oligodendrocytes, the myelin-forming cells of the central nervous system, can be generated from progenitor cell lines and assayed for their myelinating properties after transplantation. A growth-factor-dependent cell line of rat oligodendrocyte progenitors (CG4) was carried through 31-48 passages before being transplanted into normal newborn rat brain or the spinal cord of newborn myelin-deficient (md) rats. In md rat spinal cord, CG4 oligodendrocyte progenitors migrated up to 7 mm along the dorsal columns, where they divided and myelinated numerous axons 2 weeks after grafting. CG4 cells were transfected with the bacterial lacZ gene and selected for high beta-galactosidase expression. The cell migration and fate of these LacZ+ cells were analyzed after transplantation. In normal newborn brain, LacZ+ oligodendrocyte progenitors migrated along axonal tracts from the site of injection and integrated in the forming white matter. In md rats, extensive migration (up to 12 mm) was revealed by staining for beta-galactosidase activity of the intact spinal cord where many grafted cells had moved into the posterior columns. Similar migration and integration of grafted cells occurred in the spinal cord of normal myelinated rats and after a noninvasive grafting procedure. Thus, oligodendrocyte progenitors can maintain their ability to migrate and myelinate axons in vivo after multiple passages in vitro. Such progenitor cell lines can be used to study the molecular mechanisms underlying oligodendrocyte development and the repair of myelin in dysmyelinating diseases.

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Selected References

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  1. Armstrong R. C., Dorn H. H., Kufta C. V., Friedman E., Dubois-Dalcq M. E. Pre-oligodendrocytes from adult human CNS. J Neurosci. 1992 Apr;12(4):1538–1547. doi: 10.1523/JNEUROSCI.12-04-01538.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aubourg P. The leukodystrophies: a window to myelin. Nat Genet. 1993 Oct;5(2):105–106. doi: 10.1038/ng1093-105. [DOI] [PubMed] [Google Scholar]
  3. Baron-Van Evercooren A., Duhamel-Clerin E., Boutry J. M., Hauw J. J., Gumpel M. Pathways of migration of transplanted Schwann cells in the demyelinated mouse spinal cord. J Neurosci Res. 1993 Jul 1;35(4):428–438. doi: 10.1002/jnr.490350410. [DOI] [PubMed] [Google Scholar]
  4. Björklund A. Neurobiology. Better cells for brain repair. Nature. 1993 Apr 1;362(6419):414–415. doi: 10.1038/362414a0. [DOI] [PubMed] [Google Scholar]
  5. Blakemore W. F., Crang A. J. Extensive oligodendrocyte remyelination following injection of cultured central nervous system cells into demyelinating lesions in adult central nervous system. Dev Neurosci. 1988;10(1):1–11. doi: 10.1159/000111949. [DOI] [PubMed] [Google Scholar]
  6. Blakemore W. F., Franklin R. J. Transplantation of glial cells into the CNS. Trends Neurosci. 1991 Aug;14(8):323–327. doi: 10.1016/0166-2236(91)90155-n. [DOI] [PubMed] [Google Scholar]
  7. Boutry J. M., Hauw J. J., Gansmüller A., Di-Bert N., Pouchelet M., Baron-Van Evercooren A. Establishment and characterization of a mouse Schwann cell line which produces myelin in vivo. J Neurosci Res. 1992 May;32(1):15–26. doi: 10.1002/jnr.490320103. [DOI] [PubMed] [Google Scholar]
  8. Cattaneo E., McKay R. Identifying and manipulating neuronal stem cells. Trends Neurosci. 1991 Aug;14(8):338–340. doi: 10.1016/0166-2236(91)90158-q. [DOI] [PubMed] [Google Scholar]
  9. Dubois-Dalcq M., Armstrong R. The cellular and molecular events of central nervous system remyelination. Bioessays. 1990 Dec;12(12):569–576. doi: 10.1002/bies.950121203. [DOI] [PubMed] [Google Scholar]
  10. Duncan I. D., Hammang J. P., Jackson K. F., Wood P. M., Bunge R. P., Langford L. Transplantation of oligodendrocytes and Schwann cells into the spinal cord of the myelin-deficient rat. J Neurocytol. 1988 Jun;17(3):351–360. doi: 10.1007/BF01187857. [DOI] [PubMed] [Google Scholar]
  11. Duncan I. D., Hammang J. P., Trapp B. D. Abnormal compact myelin in the myelin-deficient rat: absence of proteolipid protein correlates with a defect in the intraperiod line. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6287–6291. doi: 10.1073/pnas.84.17.6287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ellis D., Malcolm S. Proteolipid protein gene dosage effect in Pelizaeus-Merzbacher disease. Nat Genet. 1994 Apr;6(4):333–334. doi: 10.1038/ng0494-333. [DOI] [PubMed] [Google Scholar]
  13. Feltri M. L., Scherer S. S., Wrabetz L., Kamholz J., Shy M. E. Mitogen-expanded Schwann cells retain the capacity to myelinate regenerating axons after transplantation into rat sciatic nerve. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8827–8831. doi: 10.1073/pnas.89.18.8827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Galileo D. S., Majors J., Horwitz A. F., Sanes J. R. Retrovirally introduced antisense integrin RNA inhibits neuroblast migration in vivo. Neuron. 1992 Dec;9(6):1117–1131. doi: 10.1016/0896-6273(92)90070-t. [DOI] [PubMed] [Google Scholar]
  15. Gansmuller A., Lachapelle F., Baron-Van Evercooren A., Hauw J. J., Baumann N., Gumpel M. Transplantations of newborn CNS fragments into the brain of shiverer mutant mice: extensive myelination by transplanted oligodendrocytes. II. Electron microscopic study. Dev Neurosci. 1986;8(4):197–207. doi: 10.1159/000112253. [DOI] [PubMed] [Google Scholar]
  16. Gogate N., Verma L., Zhou J. M., Milward E., Rusten R., O'Connor M., Kufta C., Kim J., Hudson L., Dubois-Dalcq M. Plasticity in the adult human oligodendrocyte lineage. J Neurosci. 1994 Aug;14(8):4571–4587. doi: 10.1523/JNEUROSCI.14-08-04571.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gout O., Dubois-Dalcq M. Directed migration of transplanted glial cells toward a spinal cord demyelinating lesion. Int J Dev Neurosci. 1993 Oct;11(5):613–623. doi: 10.1016/0736-5748(93)90050-n. [DOI] [PubMed] [Google Scholar]
  18. Groves A. K., Barnett S. C., Franklin R. J., Crang A. J., Mayer M., Blakemore W. F., Noble M. Repair of demyelinated lesions by transplantation of purified O-2A progenitor cells. Nature. 1993 Apr 1;362(6419):453–455. doi: 10.1038/362453a0. [DOI] [PubMed] [Google Scholar]
  19. Lachapelle F., Gumpel M., Baulac M., Jacque C., Duc P., Baumann N. Transplantation of CNS fragments into the brain of shiverer mutant mice: extensive myelination by implanted oligodendrocytes. I. Immunohistochemical studies. Dev Neurosci. 1983;6(6):325–334. doi: 10.1159/000112359. [DOI] [PubMed] [Google Scholar]
  20. Levan G., Szpirer J., Szpirer C., Klinga K., Hanson C., Islam M. Q. The gene map of the Norway rat (Rattus norvegicus) and comparative mapping with mouse and man. Genomics. 1991 Jul;10(3):699–718. doi: 10.1016/0888-7543(91)90455-n. [DOI] [PubMed] [Google Scholar]
  21. Levison S. W., Goldman J. E. Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain. Neuron. 1993 Feb;10(2):201–212. doi: 10.1016/0896-6273(93)90311-e. [DOI] [PubMed] [Google Scholar]
  22. Louis J. C., Magal E., Muir D., Manthorpe M., Varon S. CG-4, a new bipotential glial cell line from rat brain, is capable of differentiating in vitro into either mature oligodendrocytes or type-2 astrocytes. J Neurosci Res. 1992 Jan;31(1):193–204. doi: 10.1002/jnr.490310125. [DOI] [PubMed] [Google Scholar]
  23. Louis J. C., Magal E., Takayama S., Varon S. CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death. Science. 1993 Jan 29;259(5095):689–692. doi: 10.1126/science.8430320. [DOI] [PubMed] [Google Scholar]
  24. MacGregor G. R., Mogg A. E., Burke J. F., Caskey C. T. Histochemical staining of clonal mammalian cell lines expressing E. coli beta galactosidase indicates heterogeneous expression of the bacterial gene. Somat Cell Mol Genet. 1987 May;13(3):253–265. doi: 10.1007/BF01535207. [DOI] [PubMed] [Google Scholar]
  25. McKinnon R. D., Matsui T., Dubois-Dalcq M., Aaronson S. A. FGF modulates the PDGF-driven pathway of oligodendrocyte development. Neuron. 1990 Nov;5(5):603–614. doi: 10.1016/0896-6273(90)90215-2. [DOI] [PubMed] [Google Scholar]
  26. Price J., Thurlow L. Cell lineage in the rat cerebral cortex: a study using retroviral-mediated gene transfer. Development. 1988 Nov;104(3):473–482. doi: 10.1242/dev.104.3.473. [DOI] [PubMed] [Google Scholar]
  27. Raskind W. H., Williams C. A., Hudson L. D., Bird T. D. Complete deletion of the proteolipid protein gene (PLP) in a family with X-linked Pelizaeus-Merzbacher disease. Am J Hum Genet. 1991 Dec;49(6):1355–1360. [PMC free article] [PubMed] [Google Scholar]
  28. Shimohama S., Rosenberg M. B., Fagan A. M., Wolff J. A., Short M. P., Breakefield X. O., Friedmann T., Gage F. H. Grafting genetically modified cells into the rat brain: characteristics of E. coli beta-galactosidase as a reporter gene. Brain Res Mol Brain Res. 1989 Jun;5(4):271–278. doi: 10.1016/0169-328x(89)90061-2. [DOI] [PubMed] [Google Scholar]
  29. Snyder E. Y., Deitcher D. L., Walsh C., Arnold-Aldea S., Hartwieg E. A., Cepko C. L. Multipotent neural cell lines can engraft and participate in development of mouse cerebellum. Cell. 1992 Jan 10;68(1):33–51. doi: 10.1016/0092-8674(92)90204-p. [DOI] [PubMed] [Google Scholar]
  30. Trotter J., Crang A. J., Schachner M., Blakemore W. F. Lines of glial precursor cells immortalised with a temperature-sensitive oncogene give rise to astrocytes and oligodendrocytes following transplantation into demyelinated lesions in the central nervous system. Glia. 1993 Sep;9(1):25–40. doi: 10.1002/glia.440090105. [DOI] [PubMed] [Google Scholar]
  31. Utzschneider D. A., Archer D. R., Kocsis J. D., Waxman S. G., Duncan I. D. Transplantation of glial cells enhances action potential conduction of amyelinated spinal cord axons in the myelin-deficient rat. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):53–57. doi: 10.1073/pnas.91.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Warrington A. E., Barbarese E., Pfeiffer S. E. Differential myelinogenic capacity of specific developmental stages of the oligodendrocyte lineage upon transplantation into hypomyelinating hosts. J Neurosci Res. 1993 Jan;34(1):1–13. doi: 10.1002/jnr.490340102. [DOI] [PubMed] [Google Scholar]
  33. Williams B. P., Read J., Price J. The generation of neurons and oligodendrocytes from a common precursor cell. Neuron. 1991 Oct;7(4):685–693. doi: 10.1016/0896-6273(91)90381-9. [DOI] [PubMed] [Google Scholar]
  34. Wolswijk G., Noble M. Cooperation between PDGF and FGF converts slowly dividing O-2Aadult progenitor cells to rapidly dividing cells with characteristics of O-2Aperinatal progenitor cells. J Cell Biol. 1992 Aug;118(4):889–900. doi: 10.1083/jcb.118.4.889. [DOI] [PMC free article] [PubMed] [Google Scholar]

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