Skip to main content

Derivation of High-Purity Oligodendroglial Progenitors

  • Protocol
  • First Online:
Neural Cell Transplantation

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 549))

Summary

Oligodendrocytes are a type of glial cells that play a critical role in supporting the central nervous system (CNS), in particular insulating axons within the CNS by wrapping them with a myelin sheath, thereby enabling saltatory conduction. They are lost, and myelin damaged – demyelination – in a wide variety of neurological disorders. Replacing depleted cell types within demyelinated areas, however, has been shown experimentally to achieve remyelination and so help restore function. One method to produce oligodendrocytes for cellular replacement therapies is through the use of progenitor or stem cells. The ability to differentiate progenitor or stem cells into high-purity fates not only permits the generation of specific cells for transplantation therapies, but also provides powerful tools for studying cellular mechanisms of development. This chapter outlines methods of generating high-purity OPCs from multipotent neonatal progenitor or human embryonic stem cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Cervos-Navarro, J. and J. V. Lafuente (1991). “Traumatic brain injuries: structural changes.” J Neurol Sci 103(Suppl): S3–14.

    Article  PubMed  Google Scholar 

  2. Lassmann, H. (2001). “Classification of demyelinating diseases at the interface between etiology and pathogenesis.” Curr Opin Neurol 14(3): 253–8.

    Article  PubMed  CAS  Google Scholar 

  3. Engelbrecht, V., A. Scherer, et al (2002). “Diffusion-weighted MR imaging in the brain in children: findings in the normal brain and in the brain with white matter diseases.” Radiology 222(2): 410–8.

    Article  PubMed  Google Scholar 

  4. Bartzokis, G., P. H. Lu, et al (2004). “Quantifying age-related myelin breakdown with MRI: novel therapeutic targets for preventing cognitive decline and Alzheimer’s disease.” J Alzheimers Dis 6(6 Suppl): S53–9.

    PubMed  CAS  Google Scholar 

  5. Capello, E. and G. L. Mancardi (2004). “Marburg type and Balo’s concentric sclerosis: rare and acute variants of multiple sclerosis.” Neurol Sci 25(Suppl 4): S361–3.

    Article  PubMed  Google Scholar 

  6. Levin, K. H. (2004). “Variants and mimics of Guillain Barre Syndrome.” Neurologist 10(2): 61–74.

    Article  PubMed  Google Scholar 

  7. Keirstead, H. S. (2005). “Stem cells for the treatment of myelin loss.” Trends Neurosci 28(12): 677–83.

    Article  PubMed  CAS  Google Scholar 

  8. Lewis, R. A. (2005). “Chronic inflammatory demyelinating polyneuropathy and other immune-mediated demyelinating neuropathies.” Semin Neurol 25(2): 217–28.

    Article  PubMed  Google Scholar 

  9. Totoiu, M. O. and H. S. Keirstead (2005). “Spinal cord injury is accompanied by chronic progressive demyelination.” J Comp Neurol 486(4): 373–83.

    Article  PubMed  Google Scholar 

  10. De Stefano, N., P. M. Matthews, et al (1998). “Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study.” Brain 121(Pt 8): 1469–77.

    Article  PubMed  Google Scholar 

  11. Bjartmar, C., X. Yin, et al (1999). “Axonal pathology in myelin disorders.” J Neurocytol 28(4–5): 383–95.

    Article  PubMed  CAS  Google Scholar 

  12. Trapp, B. D., L. Bo, et al (1999). “Pathogenesis of tissue injury in MS lesions.” J Neuroimmunol 98(1): 49–56.

    Article  PubMed  CAS  Google Scholar 

  13. Giulian, D. (1993). “Reactive glia as rivals in regulating neuronal survival.” Glia 7(1): 102–10.

    Article  PubMed  CAS  Google Scholar 

  14. Giulian, D., M. Corpuz, et al (1993). “Reactive mononuclear phagocytes release neurotoxins after ischemic and traumatic injury to the central nervous system.” J Neurosci Res 36(6): 681–93.

    Article  PubMed  CAS  Google Scholar 

  15. Silver, J. (1994). “Inhibitory molecules in development and regeneration.” J Neurol 242(1 Suppl 1): S22–4.

    Article  PubMed  CAS  Google Scholar 

  16. Qiu, J., D. Cai, et al (2000). “Glial inhibition of nerve regeneration in the mature mammalian CNS.” Glia 29(2): 166–74.

    Article  PubMed  CAS  Google Scholar 

  17. Fournier, A. E. and S. M. Strittmatter (2001). “Repulsive factors and axon regeneration in the CNS.” Curr Opin Neurobiol 11(1): 89–94.

    Article  PubMed  CAS  Google Scholar 

  18. Charles, P., R. Reynolds, et al (2002). “Re-expression of PSA-NCAM by demyelinated axons: an inhibitor of remyelination in multiple sclerosis?” Brain 125(Pt 9): 1972–9.

    Article  PubMed  Google Scholar 

  19. Santos-Benito, F. F. and A. Ramon-Cueto (2003). “Olfactory ensheathing glia transplantation: a therapy to promote repair in the mammalian central nervous system.” Anat Rec B New Anat 271(1): 77–85.

    Article  PubMed  Google Scholar 

  20. Smith, K. J., W. I. McDonald, et al (1979). “Restoration of secure conduction by central demyelination.” Trans Am Neurol Assoc 104: 25–9.

    PubMed  CAS  Google Scholar 

  21. Waxman, S. G., D. A. Utzschneider, et al (1994). “Enhancement of action potential conduction following demyelination: experimental approaches to restoration of function in multiple sclerosis and spinal cord injury.” Prog Brain Res 100: 233–43.

    Article  PubMed  CAS  Google Scholar 

  22. Jeffery, N. D., A. J. Crang, et al (1999). “Behavioral consequences of oligodendrocyte progenitor cell transplantation into experimental demyelinating lesions in the rat spinal cord.” Eur J Neurosci 11(5): 1508–14.

    Article  PubMed  CAS  Google Scholar 

  23. Totoiu, M. O., G. I. Nistor, et al (2004). “Remyelination, axonal sparing, and locomotor recovery following transplantation of glial-committed progenitor cells into the MHV model of multiple sclerosis.” Exp Neurol 187(2): 254–65.

    Article  PubMed  CAS  Google Scholar 

  24. Keirstead, H. S., G. Nistor, et al (2005). “Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.” J Neurosci 25(19): 4694–705.

    Article  PubMed  CAS  Google Scholar 

  25. Kornek, B., M. K. Storch, et al (2000). “Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions.” Am J Pathol 157(1): 267–76.

    Article  PubMed  CAS  Google Scholar 

  26. Zhao, C., S. P. Fancy, et al (2005). “Stem cells, progenitors and myelin repair.” J Anat 207(3): 251–8.

    Article  PubMed  CAS  Google Scholar 

  27. Franklin, R. J., S. A. Bayley, et al (1996). “Transplanted CG4 cells (an oligodendrocyte progenitor cell line) survive, migrate, and contribute to repair of areas of demyelination in X-irradiated and damaged spinal cord but not in normal spinal cord.” Exp Neurol 137(2): 263–76.

    Article  PubMed  CAS  Google Scholar 

  28. Franklin, R. J. and W. F. Blakemore (1997). “Transplanting oligodendrocyte progenitors into the adult CNS.” J Anat 190(Pt 1): 23–33.

    Article  PubMed  Google Scholar 

  29. Franklin, R. J., J. M. Gilson, et al (1996). “Schwann cell-like myelination following transplantation of an olfactory bulb-ensheathing cell line into areas of demyelination in the adult CNS.” Glia 17(3): 217–24.

    Article  PubMed  CAS  Google Scholar 

  30. O’Leary, M. T. and W. F. Blakemore (1997). “Oligodendrocyte precursors survive poorly and do not migrate following transplantation into the normal adult central nervous system.” J Neurosci Res 48(2): 159–67.

    Article  PubMed  Google Scholar 

  31. Tuszynski, M. H., N. Weidner, et al (1998). “Grafts of genetically modified Schwann cells to the spinal cord: survival, axon growth, and myelination.” Cell Transplant 7(2): 187–96.

    Article  PubMed  CAS  Google Scholar 

  32. Iwashita, Y., J. W. Fawcett, et al (2000). “Schwann cells transplanted into normal and X-irradiated adult white matter do not migrate extensively and show poor long-term survival.” Exp Neurol 164(2): 292–302.

    Article  PubMed  CAS  Google Scholar 

  33. Ramon-Cueto, A. (2000). “Olfactory ensheathing glia transplantation into the injured spinal cord.” Prog Brain Res 128: 265–72.

    Article  PubMed  CAS  Google Scholar 

  34. Liu, S., Y. Qu, et al (2000). “Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation.” Proc Natl Acad Sci U S A 97(11): 6126–31.

    Article  PubMed  CAS  Google Scholar 

  35. Ogawa, Y., K. Sawamoto, et al (2002). “Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats.” J Neurosci Res 69(6): 925–33.

    Article  PubMed  CAS  Google Scholar 

  36. Ben-Hur, T., O. Einstein, et al (2003). “Transplanted multipotential neural precursor cells migrate into the inflamed white matter in response to experimental autoimmune encephalomyelitis.” Glia 41(1): 73–80.

    Article  PubMed  Google Scholar 

  37. Galli, R., A. Gritti, et al (2003). “Neural stem cells: an overview.” Circ Res 92(6): 598–608.

    Article  PubMed  CAS  Google Scholar 

  38. Iwanami, A., S. Kaneko, et al (2005). “Transplantation of human neural stem cells for spinal cord injury in primates.” J Neurosci Res 80(2): 182–90.

    Article  PubMed  CAS  Google Scholar 

  39. Nistor, G. I., M. O. Totoiu, et al (2005). “Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation.” Glia 49(3): 385–96.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hans S. Keirstead .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press, a part of Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Hatch, M.N., Nistor, G., Keirstead, H.S. (2009). Derivation of High-Purity Oligodendroglial Progenitors. In: Gordon, D., Scolding, N. (eds) Neural Cell Transplantation. Methods in Molecular Biology™, vol 549. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-931-4_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-931-4_5

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60327-930-7

  • Online ISBN: 978-1-60327-931-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics