Long-term molecular and cellular stability of human neural stem cell lines

Ana Villa, Beatriz Navarro-Galve, Carlos Bueno, Sonia Franco, María A. Blasco, Alberto Martinez-Serrano

Research output: Contribution to journalArticle

Abstract

Human Neural Stem Cells (hNSCs) are excellent candidates for in vitro and in vivo molecular, cellular, and developmental research, and also for ex-vivo gene transfer and cell therapy in the nervous system. However, hNSCs are mortal somatic cells, and thus invariably enter an irreversible growth arrest after a finite number of cell divisions in culture. It has been proposed that this is due to telomere shortening. Here, we show that long-term cultured (up to 4 years) v-myc perpetuated hNSC lines do preserve short but stable and homogeneous telomeres (TRF and Q-FISH determinations). hNSC lines (but not strains) express high levels of telomerase activity, which is activated by v-myc, as demonstrated here. Telomerase activity is not constitutive, becoming non-detectable after differentiation (in parallel to v-myc down-regulation). hNSC lines also maintain a stable cell cycle length, mitotic potential, differentiation and neuron generation capacity, and do not express senescence-associated β-galactosidase over years, as studied here. These data, collectively, help to explain the immortal nature of v-myc-perpetuated hNSC lines, and to establish them as excellent research tools for basic and applied neurobiological and translational studies.

Original languageEnglish (US)
Pages (from-to)559-570
Number of pages12
JournalExperimental cell research
Volume294
Issue number2
DOIs
StatePublished - Apr 1 2004

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Keywords

  • Human neural stem cells
  • Immortal
  • PD
  • Population doubling
  • Q-FISH
  • Quantitative fluorescent in situ hybridization
  • SA-β-gal
  • Senescence
  • Senescence associated β-galactosidase
  • TRF
  • Telomerase
  • Telomere
  • hNSCs

ASJC Scopus subject areas

  • Cell Biology

Cite this

Villa, A., Navarro-Galve, B., Bueno, C., Franco, S., Blasco, M. A., & Martinez-Serrano, A. (2004). Long-term molecular and cellular stability of human neural stem cell lines. Experimental cell research, 294(2), 559-570. https://doi.org/10.1016/j.yexcr.2003.11.025