Nature Biotechnology
17, 653 - 659 (1999)
doi:10.1038/10862
Induction of a midbrain dopaminergic phenotype in Nurr1-overexpressing
neural stem cells by type 1 astrocytesJoseph Wagner1, Peter Åkerud1, 5, Diogo S. Castro2, 5, Pontus C. Holm1, Josep M. Canals1, 4, Evan Y. Snyder3, Thomas Perlmann2
& Ernest Arenas11
Laboratory of Molecular Neurobiology, Department of
Medical Biochemistry and Biophysics, Karolinska Institute, S-17177
Stockholm, Sweden. 2
The Ludwig Institute for Cancer Research, Stockholm
Branch, Karolinska Institute, PO Box 240, S-17177 Stockholm
, Sweden. 3
Departments of Neurology and Pediatrics, Harvard Medical
School and Division of Neuroscience, Children's Hospital, 320
Longwood Ave., Boston, MA 02115.
4
Current address: Departament de Biologia Cellular i
Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona,
IDIBAPS, Casanova 143, 08036 Barcelona
, Spain. 5
These authors contributed equally to this work.
Correspondence should be addressed to Ernest Arenas ernest@cajal.mbb.ki.secell therapydifferentiationParkinson's diseaseprogenitor cellstyrosine hydroxylaseThe implementation of neural stem cell lines as a source material for brain
tissue transplants is currently limited by the ability to induce specific
neurochemical phenotypes in these cells. Here, we show that coordinated induction
of a ventral mesencephalic dopaminergic phenotype in an immortalized multipotent
neural stem cell line can be achieved in vitro. This process requires both
the overexpression of the nuclear receptor Nurr1 and factors derived
from local type 1 astrocytes. Over 80% of cells obtained by this method demonstrate
a phenotype indistinguishable from that of endogenous dopaminergic neurons.
Moreover, this procedure yields an unlimited number of cells that can engraft
in vivo and that may constitute a useful source material for neuronal replacement
in Parkinson's disease.
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