Fw: Functional Dopamine Neurons From Mouse Embryonic Stem Cells

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Functional Dopamine Neurons From Mouse Embryonic Stem Cells

> Dopamine neurons derived from embryonic stem cells function in an animal

model of Parkinson's disease

> JH Kim, JM Auerbach, JA -Gomez, I Velasco, D Gavin, N Lumelsky,

SH Lee, J Nguyen, R -Pernaute, K Bankiewicz, R McKay

> Nature 2002; 418: 50-56

>

> Mouse embryonic stem cells can be efficiently differentiated into

functional dopaminergic neurons, according to this report.

>

> Embryonic stem cells were transfected with Nurr1, a transcription factor

involved in differentiation of dopaminergic cells, to create a stable ES

cell line. Cells were then differentiated into dopamine-producing cells by a

multi-step process (see http://www.wemove.org/emove/article.asp?ID=115).

Dopaminergic phenotype was confirmed by tyrosine hydroxylase staining,

dopamine detection by HPLC, absence of inappropriate neurotransmitters,

confirmation of dopamine transporter gene expression, and other cell

type-specific markers.

>

> Cells were grafted into 6-OHDA lesioned mice. Tyrosine

hydroxylase-positive cells from the grafts showed complex morphologies and

were positive for calbindin, a marker specific for midbrain DA neurons

projecting to the striatum. In keeping with this observation, cell processes

extended into the host striatum for up to 2 mm from the graft. Cells did not

show a characteristic marker for dividing cells, and no teratomas were

observed in grafted animals.

>

> Electrophysiological measurements in slices from grafted brains indicated

functional synapses. Five of six grafted TH+ cells, but no TH- cells,

demonstrated an inhibitory post-synaptic potential characteristic of

midbrain dopamine neurons.

>

> In unilaterally lesioned animals, turning bias following amphetamine

stimulation was ipsilateral in sham-operated and non-Nurr1 grafted animals,

but was contralateral in Nurr1-grafted animals, and remained so for up to 8

weeks following the graft. Significant improvement was also seen in other

tests of motor deficits.

>

> The authors state, " The low efficiency of generation of dopamine neurons

from primary cultures of fetal, neonatal cells or adult stem cells limits

their therapeutic potential as donor cells.In contrast, embryonic stem cells

proliferate extensively and can generate dopamine neurons. Here we show that

a highly enriched population of midbrain neural stem cells can be derived

from mouse ES cells. The dopamine neurons generated by these stem cells show

electrophysiological and behavioral properties expected of neurons from the

midbrain. Our results encourage the use of ES cells in cell-replacement

therapy for Parkinson's disease. "

>

>

> Copyright 2002 WE MOVE

> Editor: (rrobinson@...)

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