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Remyelination of the Adult Demyelinated Mouse Brain by Grafted Oligodendrocyte Progenitors and the Effect of B-104 Cografts

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Abstract

The 4e transgenic mouse is characterized by overexpression of the PLP gene. Heterozygous littermates containing three PLP gene copies develop and myelinate normally. However, a progressive CNS demyelination begins at 3-4 months of age. Despite focal demyelination, these animals survive for one year with hind limb paralysis. We used this CNS demyelination model to determine if grafts of CG4 oligodendrocyte progenitors would survive and myelinate the adult CNS. Either CG4 cells, or co-grafts of CG4/B104 cells 11:1 ratio respectively) were performed. Grafted cells survived and migrated in the normal and transgenic brain. Non-treated transgenic animals revealed extensive lack of myelin. Three months post-transplant hosts with CG4 or co-transplants displayed a near normal myelin pattern. Double immunofluorescence for neurofilament and myelin basic protein revealed the presence of many naked axons in non-grafted transgenic animals. Those grafted with progenitor CG4 cells or cografts displayed a clear increase in remyelination. This data provides a new direction for the development of cell replacement therapies in demyelinating diseases.

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REFERENCES

  1. Kitagawa, K., Sinoway, M. P., Yang, C., Gould, R. M., and Colman, D. R. 1993. A proteolipid protein gene family: Expression in sharks and rays and possible evolution from an ancestral gene encoding a pore-forming polypeptide. Neuron 11:433–448.

    Google Scholar 

  2. Bizzozero, O. A., Bixler, H. A., Davis, J. D., Espinosa de los Monteros, A., and Messier, A. M. 2001. Chemical deacylation reduces the adhesive properties of proteoliped protein and leads to decompaction of the myelin sheath. J. Neurochem. 76:1129–1141.

    Google Scholar 

  3. Seitelberg, F. 1995. Neuropathology and Genetics of Pelizaeus-Merzbacher Disease. Brain Pathol. 5:267–273.

    Google Scholar 

  4. Inoue, K., Osaka, H., Imaizumi, K., Nezu, A., Takanashi, J., Arii, J., Murayama, K., Ono, J., Kikawa, Y., Mito, T., Shaffer, L. G., and Lupski, J. R. 1999. Proteolipid protein gene duplications causing Pelizaeus-Merzbacher disease: molecular mechanism and phenotypic manifestations. Ann. Neurol. 5:624–632.

    Google Scholar 

  5. Duncan, L. D. 1995. Inherited disorders of myelination of the central nervous system. Pages 990–1009, in Ransom, B. R. and Kettenmann, H. (eds.), Neuroglia, Oxford University Press, New York.

    Google Scholar 

  6. Kagawa, T., Ikenaka, K., Inoue, Y., Kuriyama, S., Tsujii, T., Nakao, J., Nakajima, K., Aruga, J., Okano, H., and Mikoshiba, K. 1994. Glial cell degeneration and hypomyelination caused by overexpression of myelin proteolipid protein gene. Neuron 13:427–442.

    Google Scholar 

  7. Gumpel, M., Gout, O., Lubetzki, C., Gansmuller, A., and Baumann, N. 1989. Myelination and remyelination in the central nervous system by transplanted oligodendrocytes using the shiverer model. Discussion on the remyelinating cell population in adult mammals. Dev. Neurosci. 11:132–139.

    Google Scholar 

  8. Blakemore, W. F., Olby, N. J., and Franklin, R. J. 1995. The use of transplanted glial cells to reconstruct glial environments in the CNS. Brain Pathol. 5:443–450.

    Google Scholar 

  9. Espinosa de los Monteros, A., Zhang, M. S., Gordon, M., Aymie, M., and de Vellis, J. 1992. Transplantation of cultured premyelinating oligodendrocytes into normal and myelin-deficient rat brain. Dev. Neurosci. 14:98–104.

    Google Scholar 

  10. Espinosa de los Monteros, A., Zhang, M., and de Vellis, J. 1993. O2A progenitor cells transplanted into the neonatal rat brain develop into oligodendrocytes but not astrocytes. Proc. Natl. Acad. Sci. USA 90:50–54.

    Google Scholar 

  11. Espinosa de los Monteros, A., Zhao, P., Huang, C., Pan, T., Chang, R., Nazarian, R., Espejo, D., and de Vellis, J. 1997. Transplantation of CG4 oligodendrocyte progenitor cells in the myelindeficient rat brain results in myelination of axons and enhanced oligodendroglial markers. J. Neurosci. Res. 50:872–887.

    Google Scholar 

  12. Espinosa de los Monteros, A., Baba, H., Zhao, M., Sosa, N., Pan, T., Huang, C. J., Nazarian, R., Chang, R., and de Vellis, J. 1997. Remyelination of the adult demyelination mouse brain by grafted oligodendrocyte progenitors. Soc. For Neurosci. 29th Ann. Meeting 214.

  13. Louis, J. C., Magal, E., Muir, D., Manthrope, M., and Varon, S. 1992. 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. 31:193–204.

    Google Scholar 

  14. Yonemasu, T., Nakahira, K., Okumura, S., Kagawa, T., Espinosa de los Monteros, A., de Vellis, J., and Ikenaka, K. 1998. The proximal promoter region is sufficient to regulate the tissue specific expression of UDP-galactose; ceramide galactosyltransferase gene. J. Neurosci. Res. 50:757–765.

    Google Scholar 

  15. Espinosa de los Monteros, A. 2001. An in vitro injury model for oligodendrocyte. Micros. Res. Tech. 52

  16. Espinosa de los Monteros, A., Kumar, S., Zhao, P., Huang, C. J., Nazarian, R., Pan, T., Scully, S., Chang, R., and de Vellis, J. 1999. Transferrin is an essential factor for myelination. Neurochem. Res. 24:235–248.

    Google Scholar 

  17. Franklin, R. J. M., Bayley, S. A., and Blakemore, W. F. 1996. Transplanted CG4 cells (an oligondendrocyte progenitor cell line) survive, migrate and contribute to repair of areas of demyelination in the x-irradiated and damaged spinal cord but not in normal spinal cord. Exp. Neurol. 137:263–276.

    Google Scholar 

  18. Tourbah, A., Linnington, C., Bachelin, C., Avellana-Adalid, V., Wekerle, H., and Baron-Van Evercooren, A. 1997. Inflammation promotes survival and migration of the CG4 oligodendrocyte progenitors transplanted in the spinal cord of both inflammatory and demyelinated EAE rats. J. Neurosci. Res. 50:853–861.

    Google Scholar 

  19. Tontsch, U., Archer, D. R., Dubois-Dalcq, M., and Duncan, I. D. 1994. Transplantation of an oligodendrocyte cell line leading to extensive myelination. Proc. Natl. Acad. Sci. USA 91:11616–11620.

    Google Scholar 

  20. Milward, E. A., Zhang, S. C., Zhao, M., Lundberg, C., Ge, B., Goetz, B. D., and Duncan, I. D. 2000. Enhanced proliferation and directed migration of oligodendroglial progenitors cografted with growth factor-secreting cells [In Process Citation] Glia 32:264–270.

    Google Scholar 

  21. Espinosa de los Monteros, A., and de Vellis, J. 1988. Myelin basic protein and transferrin characterize different subpopulations of oligodendrocytes in rat primary glial cultures. J. Neurosci. Res. 21:181–187.

    Google Scholar 

  22. Holmes, E., Hermanson, G., Cole, R., and de Vellis, J. 1988. Developmental expression of glial specific mRNAs in primary cultures of rat brain visualized by in situ hybridization. J. Neurosci. Res. 19:389–396.

    Google Scholar 

  23. Espinosa de los Monteros, A., Roussel, G., and Nussbam, J. L. 1986. A procedure for long-term culture of oligodendrocytes. Dev. Brain Res. 24:117–125.

    Google Scholar 

  24. Barres, B. A., and Raff, M. C. 1994. Control of oligodendrocyte number in the developing rat optic nerve. Neuron. 12:935–942.

    Google Scholar 

  25. Ellison, J. A., and de Vellis, J. 1994. Platelet-derived growth factor receptor is expressed by cells in the early oligodendrocyte lineage. J. Neurosci. Res. 37:116–128.

    Google Scholar 

  26. Ellison, J. A., Scully, S. A. and de Vellis, J. 1996. Evidence for neuronal regulation of oligodendrocyte development: cellular localization of platelet-derived growth factor α receptor and A-chain mRNA during cerebral cortex development in the rat. J. Neurosci. Res. 44:28–39.

    Google Scholar 

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Authors and Affiliations

  1. Mental Retardation Research Center, Neuropsychiatric Institute, Departments of Neurobiology and Psychiatry, UCLA School of Medicine, Los Angeles, CA

    A. Espinosa de los Monteros, H. Baba, P. M. Zhao, T. Pan, R. Chang & J. de Vellis

  2. National Institute for Physiological Sciences, Myodaiji, Japan

    K. Ikenaka

Authors
  1. A. Espinosa de los Monteros
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  2. H. Baba
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  3. P. M. Zhao
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  4. T. Pan
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  5. R. Chang
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  6. J. de Vellis
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  7. K. Ikenaka
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Espinosa de los Monteros, A., Baba, H., Zhao, P.M. et al. Remyelination of the Adult Demyelinated Mouse Brain by Grafted Oligodendrocyte Progenitors and the Effect of B-104 Cografts. Neurochem Res 26, 673–682 (2001). https://doi.org/10.1023/A:1010943505013

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