Purinergic Receptors in Spinal Cord-Derived Ependymal Stem/Progenitor Cells and Their Potential Role in Cell-Based Therapy for Spinal Cord Injury

Abstract

Spinal cord injury (SCI) is a major cause of paralysis with no current therapies. Following SCI, large amounts of ATP and other nucleotides are released by the traumatized tissue leading to the activation of purinergic receptors that, in coordination with growth factors, induce lesion remodeling and repair. We found that adult mammalian ependymal spinal cord-derived stem/progenitor cells (epSPCs) are capable of responding to ATP and other nucleotidic compounds, mainly through the activation of the ionotropic P2X4, P2X7, and the metabotropic P2Y1 and P2Y4 purinergic receptors. A comparative study between epSPCs from healthy rats versus epSPCis, obtained after SCI, shows a downregulation of P2Y1 receptor together with an upregulation of P2Y4 receptor in epSPCis. Moreover, spinal cord after severe traumatic contusion shows early and persistent increases in the expression of P2X4 and P2X7 receptors around the injury, which are completely reversed when epSPCis were ectopically transplanted. Since epSPCi transplantation significantly rescues neurological function after SCI in parallel to inhibition of the induced P2 ionotropic receptors, a potential avenue is open for therapeutic alternatives in SCI treatments based on purinergic receptors and the endogenous reparative modulation.