ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Prevention of senescence progression in reversibly immortalized human ensheathing glia permits their survival after deimmortalization.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 33 citations in OpenAlex.
- Conditional immortalization of olfactory ensheathing cells for intelligently regulating their proliferation state.Scientific reports · 2025Article
- Rejuvenation of human mesenchymal stem cells using a nonintegrative and conditionally removable Sendai virus vector.Scientific reports · 2024Article
- Development of aInternational journal of molecular sciences · 2024Article
- Generation of functional neurons from adult human mucosal olfactory ensheathing glia by direct lineage conversion.Cell death & disease · 2024Article
- Human placenta-derived mesenchymal stem cells stimulate neuronal regeneration by promoting axon growth and restoring neuronal activity.Frontiers in cell and developmental biology · 2023Article
- Extended lifespan of bronchial epithelial cells maintains normal cellular phenotype and transcriptome integrity.ERJ open research · 2021Article
- Generation of c-MycERScientific reports · 2019Article
- ATM/CHK/p53 Pathway Dependent Chemopreventive and Therapeutic Activity on Lung Cancer by Pterostilbene.PloS one · 2016Article
- Patient-derived olfactory mucosa for study of the non-neuronal contribution to amyotrophic lateral sclerosis pathology.Journal of cellular and molecular medicine · 2015Article
- Efficient PRNP deletion in bovine genome using gene-editing technologies in bovine cells.Prion · 2015Article
- Production of CMAH Knockout Preimplantation Embryos Derived From Immortalized Porcine Cells Via TALE Nucleases.Molecular therapy. Nucleic acids · 2014Article
- The culture of olfactory ensheathing cells (OECs)--a distinct glial cell type.Experimental neurology · 2011Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reversible immortalization holds great potential for primary tissue expansion to develop cell-based therapies as well as for basic research. Human olfactory ensheathing glia (hOEG) are promising candidates for treating spinal cord injury and for studying extrinsic neuroregenerative mechanisms. We used lentivectors with Cre/loxP technology to achieve reversible gene transfer of BMI1, SV40 large T antigen (TAg), a short hairpin RNA against p53 (shp53), and the catalytic subunit of telomerase (TERT) in primary cultures of hOEG from human donor cadaver olfactory bulbs. Several combinations of these genes were able to immortalize hOEG, conserving their antigenic markers and neuroregenerative properties but only those transduced by BMI1/TERT did not accumulate karyotypic alterations or increase senescence marker levels. Strikingly, these were also the only cells which continued to proliferate after transgene removal by Cre recombinase delivery, whereas hOEG immortalized by shp53 or TAg in combination with TERT entered into growth arrest and died. These data support the idea that immortalization and halting senescent changes are separate processes; hOEG immortalized by BMI1/TERT can revert back to their former primary cell replicative state when deimmortalized, whereas those transduced by the other combinations depend on the presence of these transgenes to maintain their aberrant proliferative state.
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