Lithium enhances proliferation and neuronal differentiation of neural progenitor cells in vitro and after transplantation into the adult rat spinal cord

Exp Neurol. 2007 Aug;206(2):296-307. doi: 10.1016/j.expneurol.2007.05.018. Epub 2007 Jun 2.

Abstract

Transplantation of neural progenitor cells (NPCs) holds great potential for the treatment of spinal cord injuries. The survival and differential fates of transplanted NPCs in the cord are key factors contributing to the success of the therapy. In this study, we investigate the effects of lithium, a widely used antidepressant drug, on the survival, proliferation and differentiation of spinal cord-derived NPCs in cultures and after transplantation into the spinal cord. Our results show that clinically relevant doses of lithium increase the proliferation of grafted NPCs at 2 weeks post-grafting and neuronal generation by grafted NPCs at 2 weeks and 4 weeks post-grafting. However, lithium does not cause preferential differentiation of NPCs into astrocytes or oligodendrocytes both in vitro and after transplantation. Our results also show that chronic treatment with lithium (up to 4 weeks) reduces microglia and macrophage activation, indicating that lithium treatment can affect the host immune response. The results of the present study provide evidence that lithium may have therapeutic potential in cell replacement strategies for CNS injury due to its ability to promote proliferation and neuronal generation of grafted NPCs and reduce the host immune reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Female
  • Gliosis / drug therapy
  • Gliosis / prevention & control
  • Graft Rejection / drug therapy
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Graft Survival / physiology
  • Lithium Compounds / pharmacology*
  • Lithium Compounds / therapeutic use
  • Neurons / drug effects*
  • Neurons / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / drug effects
  • Spinal Cord / physiology
  • Spinal Cord / surgery
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / physiopathology
  • Stem Cell Transplantation / methods*
  • Stem Cells / drug effects*
  • Stem Cells / physiology
  • Treatment Outcome

Substances

  • Lithium Compounds