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

Exp Cell Res. 2004 Apr 1;294(2):559-70. doi: 10.1016/j.yexcr.2003.11.025.


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 beta-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques / methods*
  • Cell Cycle / genetics
  • Cell Differentiation / genetics
  • Cell Line, Transformed / cytology
  • Cell Line, Transformed / enzymology*
  • Cell Survival / genetics
  • Cellular Senescence / genetics*
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins
  • Down-Regulation / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Genes, myc / genetics
  • Humans
  • Neurons / cytology
  • Neurons / enzymology*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / enzymology*
  • RNA Stability / genetics
  • RNA, Messenger / metabolism
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Telomere / enzymology*
  • Telomere / genetics


  • DNA-Binding Proteins
  • RNA, Messenger
  • DNA
  • Telomerase