Memorias de investigación
Artículos en revistas:
In vitro and in vivo enhanced generation of human A9 dopamine neurons from neural stem cells by Bcl-XL.
Año:2010
Áreas de investigación
  • Salud
Datos
Descripción
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-XL enhances the generation of DAn from VM human neural stem cells. Mechanistically, Bcl-XL not only exerts the expected antiapoptotic effect but also induces proneural (NGN2andNEUROD1) 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-XL. These effects on neurogenesis occur in parallel to a decrease in glia generation. These in vitro Bcl-XL effects are paralleled in vivo, after transplantation in hemiparkinsonian rats, where hVM1-Bcl-XL cells survive, integrate, and differentiate into DAn, alleviating behavioral motor asymmetry. Bcl-XL 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
Internacional
Si
JCR del ISI
Si
Título de la revista
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN
0021-9258
Factor de impacto JCR
5,328
Información de impacto
Volumen
285
DOI
Número de revista
13
Desde la página
9881
Hasta la página
9897
Mes
MARZO
Ranking
Esta actividad pertenece a memorias de investigación
Participantes
Grupos de investigación, Departamentos, Centros e Institutos de I+D+i relacionados
  • Creador: Grupo de Investigación: Grupo de Bioingeniería y Telemedicina