A Neuroregenerative Human Ensheathing Glia Cell Line With Conditional Rapid Growth

Ensheathing glia have been demonstrated to have neuroregenerative properties but this cell type from human sources has not been extensively studied because tissue samples are not easily obtained, primary cultures are slow growing, and human cell lines are not available. We previously isolated immort...

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Detalles Bibliográficos
Autores: García-Escudero, Vega, Gargini, Ricardo, Gallego-Hernández, M. Teresa, García-Gómez, Ana, Martín-Bermejo, María Jesús, Simón, Diana, Delicado, Alicia, Moreno-Flores, María Teresa, Ávila, Jesús, Lim, Filip
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/57130
Acceso en línea:http://hdl.handle.net/10261/57130
Access Level:acceso abierto
Palabra clave:Neuroregeneration
pinal cord injury
Cell therapies
Olfactory ensheathing glia
Reversible immortalization
Cell expansion
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spelling A Neuroregenerative Human Ensheathing Glia Cell Line With Conditional Rapid GrowthGarcía-Escudero, VegaGargini, RicardoGallego-Hernández, M. TeresaGarcía-Gómez, AnaMartín-Bermejo, María JesúsSimón, DianaDelicado, AliciaMoreno-Flores, María TeresaÁvila, JesúsLim, FilipNeuroregenerationpinal cord injuryCell therapiesOlfactory ensheathing gliaReversible immortalizationCell expansionEnsheathing glia have been demonstrated to have neuroregenerative properties but this cell type from human sources has not been extensively studied because tissue samples are not easily obtained, primary cultures are slow growing, and human cell lines are not available. We previously isolated immortalized ensheathing glia by gene transfer of BMI1 and telomerase catalytic subunit into primary cultures derived from olfactory bulbs of an elderly human cadaver donor. These cells escape the replicative senescence characteristic of primary human cells while conserving antigenic and neuroregenerative properties of ensheathing glia, but their low proliferative rate in culture complicates their utility as cell models and their application for preclinical cell therapy experiments. In this study we describe the use of a conditional SV40 T antigen (TAg) transgene to generate human ensheathing glia cell lines, which are easy to maintain due to their robust growth in culture. Although these fast growing clones exhibited polyploid karyotypes frequently observed in cells immortalized by TAg, they did not acquire a transformed phenotype, all of them maintaining neuroregenerative capacity and antigenic markers typical of ensheathing glia. These markers were also retained even after elimination of the TAg transgene using Cre/LoxP technology, although the cells died shortly after, confirming that their survival depended on the presence of the immortalizing genes. We have also demonstrated here the feasibility of using these human cell lines in animal models by genetically marking the cells with GFP and implanting them into the injured spinal cord of immunosuppressed rats. Our conditionally immortalized human ensheathing glia cell lines will thus serve as useful tools for advancing cell therapy approaches and understanding neuroregenerative mechanisms of this unique cell type.This work was supported by grants from Noscira S.A. and the Fundación Marcelino Botín. Filip Lim held Ramón y Cajal and I3 research incorporation contracts from the Spanish Ministry of Science.Peer reviewedCognizant Communication CorporationNosciraFundación BotínMinisterio de Ciencia y Tecnología (España)201220122011info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/57130reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3727/096368910X522108info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/571302026-05-22T06:33:51Z
dc.title.none.fl_str_mv A Neuroregenerative Human Ensheathing Glia Cell Line With Conditional Rapid Growth
title A Neuroregenerative Human Ensheathing Glia Cell Line With Conditional Rapid Growth
spellingShingle A Neuroregenerative Human Ensheathing Glia Cell Line With Conditional Rapid Growth
García-Escudero, Vega
Neuroregeneration
pinal cord injury
Cell therapies
Olfactory ensheathing glia
Reversible immortalization
Cell expansion
title_short A Neuroregenerative Human Ensheathing Glia Cell Line With Conditional Rapid Growth
title_full A Neuroregenerative Human Ensheathing Glia Cell Line With Conditional Rapid Growth
title_fullStr A Neuroregenerative Human Ensheathing Glia Cell Line With Conditional Rapid Growth
title_full_unstemmed A Neuroregenerative Human Ensheathing Glia Cell Line With Conditional Rapid Growth
title_sort A Neuroregenerative Human Ensheathing Glia Cell Line With Conditional Rapid Growth
dc.creator.none.fl_str_mv García-Escudero, Vega
Gargini, Ricardo
Gallego-Hernández, M. Teresa
García-Gómez, Ana
Martín-Bermejo, María Jesús
Simón, Diana
Delicado, Alicia
Moreno-Flores, María Teresa
Ávila, Jesús
Lim, Filip
author García-Escudero, Vega
author_facet García-Escudero, Vega
Gargini, Ricardo
Gallego-Hernández, M. Teresa
García-Gómez, Ana
Martín-Bermejo, María Jesús
Simón, Diana
Delicado, Alicia
Moreno-Flores, María Teresa
Ávila, Jesús
Lim, Filip
author_role author
author2 Gargini, Ricardo
Gallego-Hernández, M. Teresa
García-Gómez, Ana
Martín-Bermejo, María Jesús
Simón, Diana
Delicado, Alicia
Moreno-Flores, María Teresa
Ávila, Jesús
Lim, Filip
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Noscira
Fundación Botín
Ministerio de Ciencia y Tecnología (España)
dc.subject.none.fl_str_mv Neuroregeneration
pinal cord injury
Cell therapies
Olfactory ensheathing glia
Reversible immortalization
Cell expansion
topic Neuroregeneration
pinal cord injury
Cell therapies
Olfactory ensheathing glia
Reversible immortalization
Cell expansion
description Ensheathing glia have been demonstrated to have neuroregenerative properties but this cell type from human sources has not been extensively studied because tissue samples are not easily obtained, primary cultures are slow growing, and human cell lines are not available. We previously isolated immortalized ensheathing glia by gene transfer of BMI1 and telomerase catalytic subunit into primary cultures derived from olfactory bulbs of an elderly human cadaver donor. These cells escape the replicative senescence characteristic of primary human cells while conserving antigenic and neuroregenerative properties of ensheathing glia, but their low proliferative rate in culture complicates their utility as cell models and their application for preclinical cell therapy experiments. In this study we describe the use of a conditional SV40 T antigen (TAg) transgene to generate human ensheathing glia cell lines, which are easy to maintain due to their robust growth in culture. Although these fast growing clones exhibited polyploid karyotypes frequently observed in cells immortalized by TAg, they did not acquire a transformed phenotype, all of them maintaining neuroregenerative capacity and antigenic markers typical of ensheathing glia. These markers were also retained even after elimination of the TAg transgene using Cre/LoxP technology, although the cells died shortly after, confirming that their survival depended on the presence of the immortalizing genes. We have also demonstrated here the feasibility of using these human cell lines in animal models by genetically marking the cells with GFP and implanting them into the injured spinal cord of immunosuppressed rats. Our conditionally immortalized human ensheathing glia cell lines will thus serve as useful tools for advancing cell therapy approaches and understanding neuroregenerative mechanisms of this unique cell type.
publishDate 2011
dc.date.none.fl_str_mv 2011
2012
2012
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/57130
url http://hdl.handle.net/10261/57130
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3727/096368910X522108
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Cognizant Communication Corporation
publisher.none.fl_str_mv Cognizant Communication Corporation
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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