The activation of dormant ependymal cells following spinal cord injury

Abstract

Ependymal cells, a dormant population of ciliated progenitors found within the central canal of the spinal cord, undergo significant alterations after spinal cord injury (SCI). Understanding the molecular events that induce ependymal cell activation after SCI represents the first step toward controlling the response of the endogenous regenerative machinery in damaged tissues. This response involves the activation of specific signaling pathways in the spinal cord that promotes self-renewal, proliferation, and differentiation. We review our current understanding of the signaling pathways and molecular events that mediate the SCI-induced activation of ependymal cells by focusing on the roles of some cell adhesion molecules, cellular membrane receptors, ion channels (and their crosstalk), and transcription factors. An orchestrated response regulating the expression of receptors and ion channels fine-tunes and coordinates the activation of ependymal cells after SCI or cell transplantation. Understanding the major players in the activation of ependymal cells may help us to understand whether these cells represent a critical source of cells contributing to cellular replacement and tissue regeneration after SCI. A more complete understanding of the role and function of individual signaling pathways in endogenous spinal cord progenitors may foster the development of novel targeted therapies to induce the regeneration of the injured spinal cord.

Keywords: Activation; Ependymal cells; Regeneration; Spinal cord injury.

Fig. 1

Ependymal cells from spinal cord. Ependymal cells in central canal are marked in red in a transversal section of spinal cord and amplified for better view. Neurospheres from homogenized spinal cord tissue can grow in defined conditions. Commonly accepted but non-exclusive markers of ependymal cells in vivo and in vitro are listed accordingly

Fig. 2

In vitro organization of ependymal stem cells grown as neurospheres. GLT-1 antibody was used as marker of V-SVZ astrocytes, type B1 positioned at the core of the pinwheel structure (red), and a β-catenin antibody to delineate cell borders showing big cells in its periphery, presumably ependymal cells (green). DAPI was used to mark nuclei (blue). Arrows indicate pinwheel´s cores and dashed lines their alignments. Scale bars: 75 µm (unpublished data)