Ablation of tumor-derived stem cells transplanted to the central nervous system by genetic modification of embryonic stem cells with a suicide gene. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antiviral Agents
  • Cell Line
  • Cloning, Molecular
  • Ganciclovir
  • Genetic Vectors
  • Green Fluorescent Proteins
  • Lentivirus
  • Mice
  • Simplexvirus

MeSH Major

  • Central Nervous System
  • Embryonic Stem Cells
  • Genes, Transgenic, Suicide
  • Neoplastic Stem Cells
  • Stem Cell Transplantation
  • Thymidine Kinase

abstract

  • Embryonic stem cell (ESC)-based therapies open new possibilities as regenerative medicine for the treatment of human disease, but the presence of small numbers of undifferentiated ESCs within the transplant could lead to the development of tumors. The safety of ESC transplants would be enhanced if uncontrolled cell growth could be suppressed, using external stimuli. A lentiviral vector carrying the herpes simplex virus thymidine kinase (HSVtk) and green fluorescent protein (GFP) genes was used to genetically modify murine ESCs (HSVtk+GFP+ ESCs). In the presence of ganciclovir (GCV), 100% of HSVtk+GFP+ ESCs were killed in vitro, and 100% of flank tumors derived from HSVtk+GFP+ ESCs were eliminated. When CNS tumors were produced by the HSVtk+GFP+ ESCs, the tumor mass was completely eliminated on GCV treatment for 1 week. After GCV treatment for 3 weeks, histologic analysis showed no residual tumor cells and TaqMan realtime polymerase chain reaction analysis showed no genomic HSVtk copies or HSVtk mRNA. These data demonstrate that it is possible to use ex vivo gene transfer to modify ESCs with conditional genetic elements that can be activated in vivo to control undifferentiated ESC outgrowth and to eliminate transduced ESCs that have escaped growth control after ESC-mediated therapy to the CNS.

publication date

  • December 2007

has subject area

  • Animals
  • Antiviral Agents
  • Cell Line
  • Central Nervous System
  • Cloning, Molecular
  • Embryonic Stem Cells
  • Ganciclovir
  • Genes, Transgenic, Suicide
  • Genetic Vectors
  • Green Fluorescent Proteins
  • Lentivirus
  • Mice
  • Neoplastic Stem Cells
  • Simplexvirus
  • Stem Cell Transplantation
  • Thymidine Kinase

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1089/hum.2007.078

PubMed ID

  • 18021021

Additional Document Info

start page

  • 1182

end page

  • 1192

volume

  • 18

number

  • 12