Gene delivery to adult neural stem cells

Exp Cell Res. 2002 Sep 10;279(1):34-9. doi: 10.1006/excr.2002.5569.

Abstract

Neural stem cells may present an ideal route for gene therapy as well as offer new possibilities for the replacement of neurons lost to injury or disease. However, it has proved difficult to express ectopic genes in stem cells. We report methods to introduce genes into adult neural stem cells using viral and nonviral vectors in vitro and in vivo. Adenoviral and VSV-G-pseudotyped retroviral vectors are more efficient than plasmid transfection or VSV-G lentiviral transduction in vitro. We further show that adult neural stem cells can be directed to a neuronal fate by ectopic expression of neurogenin 2 in vitro. Plasmids can be delivered in vivo when complexed with linear polyethyleneimine, and gene expression can be targeted specifically to neural stem or progenitor cells by the use of specific promoters. These techniques may be utilized both to study the function of various genes in the differentiation of neural stem cells to specific cell fates and, ultimately, for gene therapy or to generate specific differentiated progeny for cell transplantation.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation
  • Cells, Cultured
  • Genetic Vectors
  • Lateral Ventricles / cytology
  • Lentivirus / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Neurons / physiology*
  • Plasmids
  • Retroviridae / genetics
  • Stem Cells / physiology*
  • Transfection / methods*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Nerve Tissue Proteins
  • Neurog2 protein, mouse