DanceTherParkinsonV1, Main, Exploration, bibRecord, 000252

In Vitro and in Vivo Enhanced Generation of Human A9 Dopamine Neurons from Neural Stem Cells by Bcl-XL*

Identifieur interne : 000252 ( Main/Exploration ); précédent : 000251; suivant : 000253

In Vitro and in Vivo Enhanced Generation of Human A9 Dopamine Neurons from Neural Stem Cells by Bcl-XL*

Auteurs : Elise T. Courtois ; Claudia G. Castillo ; Emma G. Seiz ; Milagros Ramos ; Carlos Bueno ; Isabel Liste ; Alberto Martínez-Serrano

Source :

The Journal of Biological Chemistry [ 0021-9258 ] ; 2010.

RBID : PMC:2843236

Abstract

Human neural stem cells derived from the ventral mesencephalon (VM) are powerful research tools and candidates for cell therapies in Parkinson disease. Previous studies with VM dopaminergic neuron (DAn) precursors indicated poor growth potential and unstable phenotypical properties. Using the model cell line hVM1 (human ventral mesencephalic neural stem cell line 1; a new human fetal VM stem cell line), we have found that Bcl-X_L enhances the generation of DAn from VM human neural stem cells. Mechanistically, Bcl-X_L not only exerts the expected antiapoptotic effect but also induces proneural (NGN2 and NEUROD1) and dopamine-related transcription factors, resulting in a high yield of DAn with the correct phenotype of substantia nigra pars compacta (SNpc). The expression of key genes directly involved in VM/SNpc dopaminergic patterning, differentiation, and maturation (EN1, LMX1B, PITX3, NURR1, VMAT2, GIRK2, and dopamine transporter) is thus enhanced by Bcl-X_L. These effects on neurogenesis occur in parallel to a decrease in glia generation. These in vitro Bcl-X_L effects are paralleled in vivo, after transplantation in hemiparkinsonian rats, where hVM1-Bcl-X_L cells survive, integrate, and differentiate into DAn, alleviating behavioral motor asymmetry. Bcl-X_L then allows for human fetal VM stem cells to stably generate mature SNpc DAn both in vitro and in vivo and is thus proposed as a helpful factor for the development of cell therapies for neurodegenerative conditions, Parkinson disease in particular.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843236

DOI: 10.1074/jbc.M109.054312
PubMed: 20106970
PubMed Central: 2843236

Affiliations:

Le document en format XML

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 Enhanced Generation of Human A9 Dopamine Neurons from Neural Stem Cells by Bcl-X<sub>L</sub>
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<front><div type="abstract" xml:lang="en"><p>Human neural stem cells derived from the ventral mesencephalon (VM) are powerful research tools and candidates for cell therapies in Parkinson disease. Previous studies with VM dopaminergic neuron (DAn) precursors indicated poor growth potential and unstable phenotypical properties. Using the model cell line hVM1 (human ventral mesencephalic neural stem cell line 1; a new human fetal VM stem cell line), we have found that Bcl-X<sub>L</sub>
 enhances the generation of DAn from VM human neural stem cells. Mechanistically, Bcl-X<sub>L</sub>
 not only exerts the expected antiapoptotic effect but also induces proneural (<italic>NGN2</italic>
 and <italic>NEUROD1</italic>
) and dopamine-related transcription factors, resulting in a high yield of DAn with the correct phenotype of substantia nigra pars compacta (SNpc). The expression of key genes directly involved in VM/SNpc dopaminergic patterning, differentiation, and maturation (<italic>EN1</italic>
, <italic>LMX1B</italic>
, <italic>PITX3</italic>
, <italic>NURR1</italic>
, <italic>VMAT2</italic>
, <italic>GIRK2</italic>
, and dopamine transporter) is thus enhanced by Bcl-X<sub>L</sub>
. These effects on neurogenesis occur in parallel to a decrease in glia generation. These <italic>in vitro</italic>
 Bcl-X<sub>L</sub>
 effects are paralleled in <italic>vivo</italic>
, after transplantation in hemiparkinsonian rats, where hVM1-Bcl-X<sub>L</sub>
 cells survive, integrate, and differentiate into DAn, alleviating behavioral motor asymmetry. Bcl-X<sub>L</sub>
 then allows for human fetal VM stem cells to stably generate mature SNpc DAn both <italic>in vitro</italic>
 and <italic>in vivo</italic>
 and is thus proposed as a helpful factor for the development of cell therapies for neurodegenerative conditions, Parkinson disease in particular.</p>
</div>
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<name sortKey="Courtois, Elise T" sort="Courtois, Elise T" uniqKey="Courtois E" first="Elise T." last="Courtois">Elise T. Courtois</name>
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<name sortKey="Martinez Serrano, Alberto" sort="Martinez Serrano, Alberto" uniqKey="Martinez Serrano A" first="Alberto" last="Martínez-Serrano">Alberto Martínez-Serrano</name>
<name sortKey="Ramos, Milagros" sort="Ramos, Milagros" uniqKey="Ramos M" first="Milagros" last="Ramos">Milagros Ramos</name>
<name sortKey="Seiz, Emma G" sort="Seiz, Emma G" uniqKey="Seiz E" first="Emma G." last="Seiz">Emma G. Seiz</name>
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Danse-thérapie et Parkinson

In Vitro and in Vivo Enhanced Generation of Human A9 Dopamine Neurons from Neural Stem Cells by Bcl-XL*

In Vitro and in Vivo Enhanced Generation of Human A9 Dopamine Neurons from Neural Stem Cells by Bcl-XL*

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Abstract

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