Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy research

A major challenge for further development of drug screening procedures, cell replacement therapies and developmental studies is the identification of expandable human stem cells able to generate the cell types needed. We have previously reported the generation of an immortalized polyclonal neural st...

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Detalles Bibliográficos
Autores: Ramos-Moreno, Tania, Lendínez, Javier G., Pino-Barrio, María José, Del Arco, Araceli, Martínez Serrano, Alberto
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/666240
Acceso en línea:http://hdl.handle.net/10486/666240
https://dx.doi.org/10.1371/journal.pone.0052714
Access Level:acceso abierto
Palabra clave:Cells, Cultured
Dopaminergic Neurons
Intermediate Filament Proteins
Mesencephalon
Rats, Sprague-Dawley
Biología y Biomedicina / Biología
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spelling Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy researchRamos-Moreno, TaniaLendínez, Javier G.Pino-Barrio, María JoséDel Arco, AraceliMartínez Serrano, AlbertoCells, CulturedDopaminergic NeuronsIntermediate Filament ProteinsMesencephalonRats, Sprague-DawleyBiología y Biomedicina / BiologíaA major challenge for further development of drug screening procedures, cell replacement therapies and developmental studies is the identification of expandable human stem cells able to generate the cell types needed. We have previously reported the generation of an immortalized polyclonal neural stem cell (NSC) line derived from the human fetal ventral mesencephalon (hVM1). This line has been biochemically, genetically, immunocytochemically and electrophysiologically characterized to document its usefulness as a model system for the generation of A9 dopaminergic neurons (DAn). Long-term in vivo transplantation studies in parkinsonian rats showed that the grafts do not mature evenly. We reasoned that diverse clones in the hVM1 line might have different abilities to differentiate. In the present study, we have analyzed 9 hVM1 clones selected on the basis of their TH generation potential and, based on the number of v-myc copies, v-myc down-regulation after in vitro differentiation, in vivo cell cycle exit, TH+ neuron generation and expression of a neuronal mature marker (hNSE), we selected two clones for further in vivo PD cell replacement studies. The conclusion is that homogeneity and clonality of characterized NSCs allow transplantation of cells with controlled properties, which should help in the design of long-term in vivo experimentsThis work was supported by grants from the Spanish Ministry of Economy and Competitiveness (formerly Science and Innovation; PLE2009-0101, SAF2010-17167), Comunidad Autónoma Madrid (S2011-BMD-2336), Instituto Salud Carlos III (RETICS TerCel, RD06/0010/0009) and European Union (Excell, NMP4-SL-2008-214706). This work was also supported by an institutional grant from Foundation Ramón Areces to the Center of Molecular Biology Severo OchoaPublic Library of ScienceDepartamento de Biología MolecularFacultad de Ciencias20122012-12-31research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/666240https://dx.doi.org/10.1371/journal.pone.0052714reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/6662402026-06-23T12:46:27Z
dc.title.none.fl_str_mv Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy research
title Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy research
spellingShingle Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy research
Ramos-Moreno, Tania
Cells, Cultured
Dopaminergic Neurons
Intermediate Filament Proteins
Mesencephalon
Rats, Sprague-Dawley
Biología y Biomedicina / Biología
title_short Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy research
title_full Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy research
title_fullStr Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy research
title_full_unstemmed Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy research
title_sort Clonal human fetal ventral mesencephalic dopaminergic neuron precursors for cell therapy research
dc.creator.none.fl_str_mv Ramos-Moreno, Tania
Lendínez, Javier G.
Pino-Barrio, María José
Del Arco, Araceli
Martínez Serrano, Alberto
author Ramos-Moreno, Tania
author_facet Ramos-Moreno, Tania
Lendínez, Javier G.
Pino-Barrio, María José
Del Arco, Araceli
Martínez Serrano, Alberto
author_role author
author2 Lendínez, Javier G.
Pino-Barrio, María José
Del Arco, Araceli
Martínez Serrano, Alberto
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Departamento de Biología Molecular
Facultad de Ciencias
dc.subject.none.fl_str_mv Cells, Cultured
Dopaminergic Neurons
Intermediate Filament Proteins
Mesencephalon
Rats, Sprague-Dawley
Biología y Biomedicina / Biología
topic Cells, Cultured
Dopaminergic Neurons
Intermediate Filament Proteins
Mesencephalon
Rats, Sprague-Dawley
Biología y Biomedicina / Biología
description A major challenge for further development of drug screening procedures, cell replacement therapies and developmental studies is the identification of expandable human stem cells able to generate the cell types needed. We have previously reported the generation of an immortalized polyclonal neural stem cell (NSC) line derived from the human fetal ventral mesencephalon (hVM1). This line has been biochemically, genetically, immunocytochemically and electrophysiologically characterized to document its usefulness as a model system for the generation of A9 dopaminergic neurons (DAn). Long-term in vivo transplantation studies in parkinsonian rats showed that the grafts do not mature evenly. We reasoned that diverse clones in the hVM1 line might have different abilities to differentiate. In the present study, we have analyzed 9 hVM1 clones selected on the basis of their TH generation potential and, based on the number of v-myc copies, v-myc down-regulation after in vitro differentiation, in vivo cell cycle exit, TH+ neuron generation and expression of a neuronal mature marker (hNSE), we selected two clones for further in vivo PD cell replacement studies. The conclusion is that homogeneity and clonality of characterized NSCs allow transplantation of cells with controlled properties, which should help in the design of long-term in vivo experiments
publishDate 2012
dc.date.none.fl_str_mv 2012
2012-12-31
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10486/666240
https://dx.doi.org/10.1371/journal.pone.0052714
url http://hdl.handle.net/10486/666240
https://dx.doi.org/10.1371/journal.pone.0052714
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Biblos-e Archivo. Repositorio Institucional de la UAM
instname:Universidad Autónoma de Madrid
instname_str Universidad Autónoma de Madrid
reponame_str Biblos-e Archivo. Repositorio Institucional de la UAM
collection Biblos-e Archivo. Repositorio Institucional de la UAM
repository.name.fl_str_mv
repository.mail.fl_str_mv
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