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Stem cells for the treatment of neurological disorders

Abstract

Many common neurological disorders, such as Parkinson's disease, stroke and multiple sclerosis, are caused by a loss of neurons and glial cells. In recent years, neurons and glia have been generated successfully from stem cells in culture, fuelling efforts to develop stem-cell-based transplantation therapies for human patients. More recently, efforts have been extended to stimulating the formation and preventing the death of neurons and glial cells produced by endogenous stem cells within the adult central nervous system. The next step is to translate these exciting advances from the laboratory into clinically useful therapies.

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Figure 1: Application of stem cells for neurological disorders.
Figure 2: Transplantation of stem cells into injured brain.

References

  1. Lindvall, O., Kokaia, Z. & Martinez-Serrano, A. Stem cell therapy for human neurodegenerative disorders—how to make it work. Nature Med. 10 (suppl.), S42–S50 (2004).

    Article  PubMed  Google Scholar 

  2. Dezawa, M. et al. Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J. Clin. Invest. 113, 1701–1710 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Takagi, Y. et al. Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model. J. Clin. Invest. 115, 102–109 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Mendez, I. et al. Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease. Brain 128, 1498–1510 (2005).

    Article  PubMed  Google Scholar 

  5. Perrier, A. L. et al. Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc. Natl Acad. Sci. USA 101, 12543–12548 (2004).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  6. Piccini, P. et al. Factors affecting the clinical outcome after neural transplantation in Parkinson's disease. Brain 128, 2977–2986 (2005).

    Article  PubMed  Google Scholar 

  7. Behrstock, S. et al. Human neural progenitors deliver glial cell line-derived neurotrophic factor to parkinsonian rodents and aged primates. Gene Ther. 13, 379–388 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Kelly, S. et al. Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex. Proc. Natl Acad. Sci. USA 101, 11839–11844 (2004).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hayashi, J. et al. Primate embryonic stem cell-derived neuronal progenitors transplanted into ischemic brain. J. Cereb. Blood Flow Metab. published online 4 January 2006 (doi:10.1038/sj.jcbfm.9600247).

  10. Ikeda, R. et al. Transplantation of neural cells derived from retinoic acid-treated cynomolgus monkey embryonic stem cells successfully improved motor function of hemiplegic mice with experimental brain injury. Neurobiol. Dis. 20, 38–48 (2005).

    Article  CAS  PubMed  Google Scholar 

  11. Wei, L. et al. Transplantation of embryonic stem cells overexpressing Bcl-2 promotes functional recovery after transient cerebral ischemia. Neurobiol. Dis. 19, 183–193 (2005).

    Article  CAS  PubMed  Google Scholar 

  12. Thored, P. et al. Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells 24, 739–747 (2006).

    Article  CAS  PubMed  Google Scholar 

  13. Ryu, J. K. et al. Proactive transplantation of human neural stem cells prevents degeneration of striatal neurons in a rat model of Huntington disease. Neurobiol. Dis. 16, 68–77 (2004).

    Article  CAS  PubMed  Google Scholar 

  14. McBride, J. L. et al. Human neural stem cell transplants improve motor function in a rat model of Huntington's disease. J. Comp. Neurol. 475, 211–219 (2004).

    Article  PubMed  Google Scholar 

  15. Wichterle, H., Lieberam, I., Porter, J. A. & Jessell, T. M. Directed differentiation of embryonic stem cells into motor neurons. Cell 110, 385–397 (2002).

    Article  CAS  PubMed  Google Scholar 

  16. Li, X. J. et al. Specification of motoneurons from human embryonic stem cells. Nature Biotechnol. 23, 215–221 (2005).

    Article  Google Scholar 

  17. Harper, J. M. et al. Axonal growth of embryonic stem cell-derived motoneurons in vitro and in motoneuron-injured adult rats. Proc. Natl Acad. Sci. USA 101, 7123–7128 (2004).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  18. Miles, G. B. et al. Functional properties of motoneurons derived from mouse embryonic stem cells. J. Neurosci. 24, 7848–7858 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kerr, D. A. et al. Human embryonic germ cell derivatives facilitate motor recovery of rats with diffuse motor neuron injury. J. Neurosci. 23, 5131–5140 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Klein, S. M. et al. GDNF delivery using human neural progenitor cells in a rat model of ALS. Hum. Gene Ther. 16, 509–521 (2005).

    Article  CAS  PubMed  Google Scholar 

  21. Tuszynski, M. H. et al. A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nature Med. 11, 551–555 (2005).

    Article  CAS  PubMed  Google Scholar 

  22. Windrem, M. S. et al. Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nature Med. 10, 93–97 (2004).

    Article  CAS  PubMed  Google Scholar 

  23. Back, S. A. et al. Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation. Nature Med. 11, 966–972 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Nistor, G. I., Totoiu, M. O., Haque, N., Carpenter, M. K. & Keirstead, H. S. Human embryonic stem cells differentiate into oligodendrocytes in high purity and myelinate after spinal cord transplantation. Glia 49, 385–396 (2005).

    Article  PubMed  Google Scholar 

  25. Pluchino, S. et al. Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 422, 688–694 (2003).

    Article  ADS  CAS  PubMed  Google Scholar 

  26. Pluchino, S. et al. Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature 436, 266–271 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  27. McDonald, J. W. et al. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nature Med. 5, 1410–1412 (1999).

    Article  CAS  PubMed  Google Scholar 

  28. Ogawa, Y. et al. 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, 925–933 (2002).

    Article  CAS  PubMed  Google Scholar 

  29. Cummings, B. J. et al. Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice. Proc. Natl Acad. Sci. USA 102, 14069–14074 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hofstetter, C. P. et al. Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome. Nature Neurosci. 8, 346–353 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. Yang, H. et al. Endogenous neurogenesis replaces oligodendrocytes and astrocytes after primate spinal cord injury. J. Neurosci. 26, 2157–2166 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Keirstead, H. S. et al. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. J. Neurosci. 25, 4694–4705 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Olle Lindvall.

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Lindvall, O., Kokaia, Z. Stem cells for the treatment of neurological disorders. Nature 441, 1094–1096 (2006). https://doi.org/10.1038/nature04960

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