Elsevier

Experimental Neurology

Volume 177, Issue 1, September 2002, Pages 50-60
Experimental Neurology

Regular Article
Neural Stem Cells Spontaneously Express Dopaminergic Traits after Transplantation into the Intact or 6-Hydroxydopamine-Lesioned Rat

https://doi.org/10.1006/exnr.2002.7989Get rights and content

Abstract

The ability to differentiate neural stem cells (NSCs) into dopamine neurons is fundamental to their role in cell replacement therapies for neurodegenerative disorders such as Parkinson's disease. We show here that when a clonal line (C17.2) of undifferentiated NSCs is transplanted into the intact or 6-hydroxydopamine-lesioned striatum, cells withdraw from the cell cycle (BrdU), migrate extensively in the host striatum, and express markers associated with neuronal (β-tubulin III+, NSE+, NeuN+) but not glial (GFAP, MBP, A2B5) differentiation. Importantly, by 2–5 weeks postgrafting, in the majority of these transplants, nearly all engrafted cells express the dopamine-synthesizing enzymes tyrosine hydroxylase and aromatic l-amino decarboxylase, sometimes resulting in changes in motor behavior. In contrast, no NSCs stain for dopamine-β-hydroxylase, choline acetyltransferase, glutamic acid decarboxylase, or serotonin. We conclude that, following transplantation into the intact or 6-hydroxydopamine-lesioned rat, the adult brain contains intrinsic cues sufficient to direct the specific expression of dopaminergic traits in immature multipotential neural stem cells.

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    To whom correspondence should be addressed at the Department of Neurology, Thomas Jefferson University Medical College, Suite 501, College Building, 1025 Walnut Street, Philadelphia, PA 19107. Fax: (215) 955-2993. E-mail: [email protected].

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