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

• Published in: International journal of molecular sciences 2021-01, Vol.22 (2), p.713
• Main Authors: Herrera, Alejandro, Morcuende, Sara, Talaverón, Rocío, Benítez-Temiño, Beatriz, Pastor, Angel M, Matarredona, Esperanza R
• Format: Article
• Language: English
• Subjects: Adenosine; Animals; Apoptosis; Apoptosis - drug effects; Biological effects; Brain; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell therapy; Cells (biology); Cells, Cultured; Connexin 43; Epidermal growth factor; Female; Growth factors; Hippocampus - drug effects; Hippocampus - metabolism; Lateral Ventricles - drug effects; Lateral Ventricles - metabolism; Male; Nervous system; neural progenitor cells; Neural stem cells; Neural Stem Cells - drug effects; Neural Stem Cells - metabolism; Neurons; Neurospheres; Progenitor cells; Proteins; Purine receptors; Purinergic Antagonists - pharmacology; purinergic signaling; Rats; Rats, Wistar; Receptor mechanisms; Receptors, Purinergic - metabolism; Signal Transduction - drug effects; Stem Cells - drug effects; Stem Cells - metabolism; Subventricular zone; Suramin; Suramin - pharmacology; Survival; Transplantation; Transplants & implants; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22020713

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.