A conditionally immortal clonal stem cell line from human cortical neuroepithelium for the treatment of ischemic stroke

Exp Neurol. 2006 May;199(1):143-55. doi: 10.1016/j.expneurol.2005.12.011. Epub 2006 Feb 7.

Abstract

Transplantation of neural stem cells into the brain is a novel approach to the treatment of chronic stroke disability. For clinical application, safety and efficacy of defined, stable cell lines produced under GMP conditions are required. To this end, a human neural stem cell line, CTX0E03, was derived from human somatic stem cells following genetic modification with a conditional immortalizing gene, c-mycER(TAM). This transgene generates a fusion protein that stimulates cell proliferation in the presence of a synthetic drug 4-hydroxy-tamoxifen (4-OHT). The cell line is clonal, expands rapidly in culture (doubling time 50-60 h) and has a normal human karyotype (46 XY). In the absence of growth factors and 4-OHT, the cells undergo growth arrest and differentiate into neurons and astrocytes. Transplantation of CTX0E03 in a rat model of stroke (MCAo) caused statistically significant improvements in both sensorimotor function and gross motor asymmetry at 6-12 weeks post-grafting. In addition, cell migration and long-term survival in vivo were not associated with significant cell proliferation. These data indicate that CTX0E03 has the appropriate biological and manufacturing characteristics necessary for development as a therapeutic cell line.

Publication types

  • Comparative Study

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Cell Differentiation / physiology
  • Cell Movement
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / embryology
  • Clone Cells
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Fetus
  • Humans
  • Hydroxytestosterones / pharmacology
  • Infarction, Middle Cerebral Artery / surgery*
  • Male
  • Motor Activity / physiology
  • Neuroepithelial Cells / cytology
  • Neuroepithelial Cells / physiology*
  • RNA, Messenger / biosynthesis
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Stem Cell Transplantation* / methods
  • Stem Cells / physiology*
  • Telomerase / drug effects
  • Telomerase / metabolism
  • Time Factors
  • Transduction, Genetic / methods

Substances

  • Hydroxytestosterones
  • RNA, Messenger
  • 4,17 beta-dihydroxy-4-androstene-3-one
  • Telomerase