Observatorio de I+D+i UPM

Memorias de investigación
Research Publications in journals:
In vitro and in vivo enhanced generation of human A9 dopamine neurons from neural stem cells by Bcl-XL.
Year:2010
Research Areas
  • Health
Information
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-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
International
Si
JCR
Si
Title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISBN
0021-9258
Impact factor JCR
5,328
Impact info
Volume
285
Journal number
13
From page
9881
To page
9897
Month
MARZO
Ranking
Participants
  • Autor: Milagros Ramos Gomez (UPM)
Research Group, Departaments and Institutes related
  • Creador: Grupo de Investigación: Grupo de Bioingeniería y Telemedicina
S2i 2020 Observatorio de investigación @ UPM con la colaboración del Consejo Social UPM
Cofinanciación del MINECO en el marco del Programa INNCIDE 2011 (OTR-2011-0236)
Cofinanciación del MINECO en el marco del Programa INNPACTO (IPT-020000-2010-22)