Purinergic Receptor Blockade with Suramin Increases Survival of Postnatal Neural Progenitor Cells In Vitro

Int J Mol Sci. 2021 Jan 12;22(2):713. doi: 10.3390/ijms22020713.

Abstract

Neural progenitor cells (NPCs) are self-renewing and multipotent cells that persist in the postnatal and adult brain in the subventricular zone and the hippocampus. NPCs can be expanded in vitro to be used in cell therapy. However, expansion is limited, since the survival and proliferation of adult NPCs decrease with serial passages. Many signaling pathways control NPC survival and renewal. Among these, purinergic receptor activation exerts differential effects on the biology of adult NPCs depending on the cellular context. In this study, we sought to analyze the effect of a general blockade of purinergic receptors with suramin on the proliferation and survival of NPCs isolated from the subventricular zone of postnatal rats, which are cultured as neurospheres. Treatment of neurospheres with suramin induced a significant increase in neurosphere diameter and in NPC number attributed to a decrease in apoptosis. Proliferation and multipotency were not affected. Suramin also induced an increase in the gap junction protein connexin43 and in vascular endothelial growth factor, which might be involved in the anti-apoptotic effect. Our results offer a valuable tool for increasing NPC survival before implantation in the lesioned brain and open the possibility of using this drug as adjunctive therapy to NPC transplantation.

Keywords: apoptosis; cell therapy; neural progenitor cells; purinergic signaling; suramin.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects*
  • Cells, Cultured
  • Female
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Lateral Ventricles / drug effects
  • Lateral Ventricles / metabolism
  • Male
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / metabolism
  • Purinergic Antagonists / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Purinergic / metabolism*
  • Signal Transduction / drug effects
  • Stem Cells / drug effects*
  • Stem Cells / metabolism
  • Suramin / pharmacology*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Purinergic Antagonists
  • Receptors, Purinergic
  • Vascular Endothelial Growth Factor A
  • Suramin