Prevention of senescence progression in reversibly immortalized human ensheathing glia permits their survival after deimmortalization.

Molecular Therapy : the Journal of the American Society of Gene Therapy
Vega García-EscuderoFilip Lim

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...Continue Reading

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Citations

Jan 26, 2012·Zygote : the Biology of Gametes and Early Embryos·JoonHo MoonGoo Jang
Jan 29, 2014·Molekuliarnaia biologiia·N A KovalenkoT F Kovalenko
Apr 20, 2010·Brain Research·Catherine Anne GorriePhil M E Waite
Mar 27, 2015·Journal of Cellular and Molecular Medicine·Vega García-EscuderoFilip Lim
Sep 21, 2010·Experimental Neurology·Giles W PlantSeok Voon Lee
Sep 8, 2010·Experimental Neurology·Jennifer R Higginson, Susan C Barnett
Jun 28, 2016·Molecular and Cellular Neurosciences·Johana Tello VelasquezJames A St John
Aug 20, 2010·Cell Transplantation·Vega García-EscuderoFilip Lim
Jan 14, 2018·Glia·Rosa M GómezM Teresa Moreno-Flores

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