Abstract:
: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.
journal_name
Cell Transplantjournal_title
Cell transplantationauthors
García-Escudero V,Gargini R,Gallego-Hernández MT,García-Gómez A,Martín-Bermejo MJ,Simón D,Delicado A,Moreno-Flores MT,Avila J,Lim Fdoi
10.3727/096368910X522108subject
Has Abstractpub_date
2011-01-01 00:00:00pages
153-66issue
2eissn
0963-6897issn
1555-3892pii
ct0009garciaescuderojournal_volume
20pub_type
杂志文章abstract::Potential labels for identifying embryonic raphe neurons and a clonal, neuronally differentiating, raphe-derived cell line, RN33B, in CNS transplantation studies were tested by first characterizing the labels in vitro. The labels that were tested included 4',6-diamidino-2-phenylindole hydrochloride, 1,1'-dioctadecyl-3...
journal_title:Cell transplantation
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abstract::Stem cells are unique cells in the ability that can self-renew and differentiate into a wide variety of cell types, suggesting that a specific molecular control network underlies these features. To date, stem cells have been applied to many clinical therapeutic approaches. For example, hematopoietic stem cells (HSCs) ...
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