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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2011-03-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368910X522108 |
| _version_ | 1818912899285909504 |
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| author | Vega García-Escudero Ricardo Gargini María Teresa Gallego-Hernández Ana García-Gómez María Jesús Martín-Bermejo Diana Simón Alicia Delicado María Teresa Moreno-Flores Jesús Ávila Filip Lim |
| author_facet | Vega García-Escudero Ricardo Gargini María Teresa Gallego-Hernández Ana García-Gómez María Jesús Martín-Bermejo Diana Simón Alicia Delicado María Teresa Moreno-Flores Jesús Ávila Filip Lim |
| author_sort | Vega García-Escudero |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T23:21:55Z |
| format | Article |
| id | doaj.art-23ffe681974549f4bf9ed2e4d3d0b222 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-19T23:21:55Z |
| publishDate | 2011-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-23ffe681974549f4bf9ed2e4d3d0b2222022-12-21T20:01:57ZengSAGE PublishingCell Transplantation0963-68971555-38922011-03-012010.3727/096368910X522108A Neuroregenerative Human Ensheathing Glia Cell Line with Conditional Rapid GrowthVega García-Escudero0Ricardo Gargini1María Teresa Gallego-Hernández2Ana García-Gómez3María Jesús Martín-Bermejo4Diana Simón5Alicia Delicado6María Teresa Moreno-Flores7Jesús Ávila8Filip Lim9Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Cantoblanco, Madrid, SpainCentro de Biología Molecular Severo Ochoa (CSIC-UAM), Cantoblanco, Madrid, SpainCentro de Biología Molecular Severo Ochoa (CSIC-UAM), Cantoblanco, Madrid, SpainCentro de Biología Molecular Severo Ochoa (CSIC-UAM), Cantoblanco, Madrid, SpainCentro de Biología Molecular Severo Ochoa (CSIC-UAM), Cantoblanco, Madrid, SpainCentro de Biología Molecular Severo Ochoa (CSIC-UAM), Cantoblanco, Madrid, SpainServicio de Genética Médica, Hospital La Paz, Madrid, SpainCentro de Biología Molecular Severo Ochoa (CSIC-UAM), Cantoblanco, Madrid, SpainCentro de Biología Molecular Severo Ochoa (CSIC-UAM), Cantoblanco, Madrid, SpainDepartamento de Biología Molecular, Universidad Autónoma de Madrid, Cantoblanco, Madrid, SpainEnsheathing 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.https://doi.org/10.3727/096368910X522108 |
| spellingShingle | Vega García-Escudero Ricardo Gargini María Teresa Gallego-Hernández Ana García-Gómez María Jesús Martín-Bermejo Diana Simón Alicia Delicado María Teresa Moreno-Flores Jesús Ávila Filip Lim A Neuroregenerative Human Ensheathing Glia Cell Line with Conditional Rapid Growth Cell Transplantation |
| title | 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_short | A Neuroregenerative Human Ensheathing Glia Cell Line with Conditional Rapid Growth |
| title_sort | neuroregenerative human ensheathing glia cell line with conditional rapid growth |
| url | https://doi.org/10.3727/096368910X522108 |
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