Transplantation of Neural Stem/Progenitor Cells into Developing and Adult CNS

  • Tong Zheng
  • Gregory P. Marshall IIII
  • K. Amy Chen
  • Eric D. Laywell
Part of the Methods in Molecular Biology book series (MIMB, volume 482)


Neural transplantation has been a long-standing goal for the treatment of neurological injury and disease. The recent discovery of persistent pools of neural stem cells within the adult mammalian brain has reignited interest in transplant therapeutics. Since neural stem cells are self-renewing, it may be possible to culture and expand neural stem cells and their progenitor cell progeny to sufficient numbers for use in autologous, self-repair strategies. Such approaches will require optimized cultivation protocols, as well as extensive testing of candidate donor cells to assess their capacity for engraftment, survival, and integration. In this chapter, we describe the transplantation of neural stem/progenitor cells—cultivated as either neurospheres or neurogenic astrocyte monolayers—into the persistently neurogenic olfactory bulb system of the adult mouse forebrain, and into the cerebellum of neonatal mutant mice.

Key words

Transplantation neurosphere neural stem cell neurogenic astrocyte subependymal zone 


  1. 1.
    Bjorklund, A., Stenevi, U. (1979) Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Res. 177:555–60.CrossRefPubMedGoogle Scholar
  2. 2.
    Madrazo, I., Drucker-Colin, R., Diaz, V., Martinez-Mata J., Torres, C., Becerri, J.J. (1987) Open microsurgical autograft of adrenal medulla to the right caudate nucleus in two patients with intractable Parkinson's disease. N Engl J Med. 316:831–4.CrossRefPubMedGoogle Scholar
  3. 3.
    Fernandez-Espejo, E., Armengol, J.A., Flores, J.A., Galan-Rodriguez, B., Ramiro, S. (2005) Cells of the sympathoadrenal lineage: biological properties as donor tissue for cell-replacement therapies for Parkinson's disease. Brain Res Brain Res Rev. 49:343–54.CrossRefPubMedGoogle Scholar
  4. 4.
    Winkler, C., Kirik, D., Bjorklund, A. (2005) Cell transplantation in Parkinson’s disease: how can we make it work? Trends Neurosci. 28:86–92.CrossRefPubMedGoogle Scholar
  5. 5.
    Correia, A.S., Anisimov, S.V., Li, J-Y., Brundin, P. (2005) Stem cell-based therapy for Parkinson’s disease. Ann Med. 37:487–98.CrossRefPubMedGoogle Scholar
  6. 6.
    Freed, W.J., Cannon-Spoor, H.E., Krauthammer, E. (1987) Intrastriatal adrenal medulla grafts in rats. Long-term survival and behavioral effects. J Neurosurg. 65:664–70.Google Scholar
  7. 7.
    Reynolds, B.A., Weiss, S. (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–10.CrossRefPubMedGoogle Scholar
  8. 8.
    Reynolds, B.A., Rietze, R.L. (2005) Neural stem cells and neurospheres—re-evaluating the relationship. Nat Meth. 2:333–6.CrossRefGoogle Scholar
  9. 9.
    Laywell, E.D., Rakic, P., Kukekov, V.G., Holland, E.C., Steindler, D.A. (2000) Identification of a multipotent astrocytic stem cell in the immature and adult mouse brain. Proc Natl Acad Sci USA. 97:13883–8.CrossRefPubMedGoogle Scholar
  10. 10.
    Scheffler, B., Walton, N.M., Lin, D.D., Goetz, A.K., Enikolopov, G., Roper, S.N., Steindler, D.A. (2005). Phenotypic and functional characterization of adult brain neuropoiesis. Proc Natl Acad Sci USA. 102:9353–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Zheng, T., Steindler, D.A., Laywell, E.D. (2002) Transplantation of an indigenous neural stem cell population leading to hyperplasia and atypical integration. Clon Stem Cells 4:3–8.CrossRefGoogle Scholar
  12. 12.
    Zheng, T., Marshall, G.P., II, Laywell, E.D., Steindler, D.A. (2006a). Neurogenic astrocytes transplanted into the adult mouse lateral ventricle contribute to olfactory neurogenesis, and reveal a novel intrinsic subependymal neuron. Neurosci. 142:175–85.Google Scholar
  13. 13.
    Deng, J., Steindler, D.A., Petersen, B.E., Laywell, E.D. (2003). Neural trans-differentiation potential of hepatic oval cells in the neonatal mouse brain. Exp Neurol. 182:373–382.CrossRefPubMedGoogle Scholar
  14. 14.
    Marshall, G.P., II, Scott, E.W., Zheng, T., Laywell, E.D., Steindler, D.A. (2005). Ionizing irradiation enhances the engraftment of transplanted in vitro-derived neural multipotent astrocytic stem cells. Stem Cells 23:1276–85.CrossRefPubMedGoogle Scholar
  15. 15.
    Zheng, T., Rossignol, C., Leibovici, A., Anderson, K.J., Steindler, D.A., Weiss, M.D. (2006) Transplantation of multipotent astrocytic stem cells into a rat model of neonatal hypoxic-ischemic encephalopathy. Brain Res. 1112:99–105.CrossRefPubMedGoogle Scholar
  16. 16.
    Laywell, E.D., Kukekov, V.G., Suslov, O., Zheng, T., Steindler, D.A. (2002) Production and analysis of neurospheres from acutely dissociated and postmortem CNS specimens. Meth Mol Biol. 198:15–27.Google Scholar
  17. 17.
    Seaberg, R.M., van der Kooy, D. (2003) Stem and progenitor cells: the premature desertion of rigorous definitions. Trends Neurosci. 26:125–31.CrossRefPubMedGoogle Scholar
  18. 18.
    Phifer, C.B., Terry, L.M. (1986). Use of hypothermia for general anesthesia in preweanling rodents. Physiol Behav. 38:887–90.CrossRefPubMedGoogle Scholar
  19. 19.
    Walton, N.M., Sutter, B.M., Laywell, E.D., Levkoff, L.H., Kearns, S.M., Marshall, G.P., II, Scheffler, B., Steindler, D.A. (2006). Microglia instruct subventricular zone neurogenesis. GLIA 54:815–25.CrossRefPubMedGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Tong Zheng
    • 1
  • Gregory P. Marshall IIII
    • 2
  • K. Amy Chen
    • 1
  • Eric D. Laywell
    • 3
  1. 1.Department of NeuroscienceMcKnight Brain Institute, University of FloridaGainesvilleUSA
  2. 2.Department of Anatomy & Cell BiologyMcKnight Brain Institute, University of FloridaGainesvilleUSA
  3. 3.Department of Anatomy & Cell BiologyCollege of Medicine, University of FloridaGainesvilleUSA

Personalised recommendations