The ependymal region of the adult human spinal cord differs from other species and shows ependymoma-like features

Abstract

Several laboratories have described the existence of undifferentiated precursor cells that may act like stem cells in the ependyma of the rodent spinal cord. However, there are reports showing that this region is occluded and disassembled in humans after the second decade of life, although this has been largely ignored or interpreted as a post-mortem artefact. To gain insight into the patency, actual structure, and molecular properties of the adult human spinal cord ependymal region, we followed three approaches: (i) with MRI, we estimated the central canal patency in 59 control subjects, 99 patients with traumatic spinal cord injury, and 26 patients with non-traumatic spinal cord injuries. We observed that the central canal is absent from the vast majority of individuals beyond the age of 18 years, gender-independently, throughout the entire length of the spinal cord, both in healthy controls and after injury; (ii) with histology and immunohistochemistry, we describe morphological properties of the non-lesioned ependymal region, which showed the presence of perivascular pseudorosettes, a common feature of ependymoma; and (iii) with laser capture microdissection, followed by TaqMan® low density arrays, we studied the gene expression profile of the ependymal region and found that it is mainly enriched in genes compatible with a low grade or quiescent ependymoma (53 genes); this region is enriched only in 14 genes related to neurogenic niches. In summary, we demonstrate here that the central canal is mainly absent in the adult human spinal cord and is replaced by a structure morphologically and molecularly different from that described for rodents and other primates. The presented data suggest that the ependymal region is more likely to be reminiscent of a low-grade ependymoma. Therefore, a direct translation to adult human patients of an eventual therapeutic potential of this region based on animal models should be approached with caution.

Ependymal cell contribution to scar formation after spinal cord injury is minimal, local and dependent on direct ependymal injury

“…We noted that previous studies based their conclusions that ependymal cells give rise to the majority of scar-forming astrocytes in SCI lesions on the assertion that the majority of those putative astrocytes were “Sox9 positive, vimentin positive and GFAP negative”222324. However, both Sox93637 and vimentin323839 are highly expressed by ependymal cells, raising questions as to the validity of using these markers in the absence of GFAP to identify ependymal progeny as astrocytes. In addition, there is no precedent in the literature for the existence of scar-forming reactive astrocytes that do not express GFAP.…”

“…To identify ependyma we used CD1333132 and vimentin3839, while reactive astrocytes were identified by both GFAP and Aldh1l1 labeling. GFAP was first isolated from CNS lesions40 and has over many decades of research become the canonical maker of astrocyte reactivity in response to CNS damage.…”

“…To identify specific cell types, we used multiple well-established markers to identify ependyma, Sox9, CD133, vimentin3132363839 or astrocytes, GFAP, Aldh1l164142434445. Inexplicably, the previous proposals that the majority of neuroprotective reactive astrocytes derived from ependymal cell progeny after SCI were based on the contention that these putative astrocytes were “Sox9 positive, vimentin positive and GFAP negative”22232425.…”

The Human Central Canal of the Spinal Cord: A Comprehensive Review of its Anatomy, Embryology, Molecular Development, Variants, and Pathology

“…Garcia-Ovejero, et al [41] were able to demonstrate that the adult human central canal displays at least three common characteristics distinct from other species: first, a gliosis formed by a dense mesh of glial fibrillary acidic protein-positive ( GFAP+) astrocytic processes. A second feature is the presence of protoplasmic cells or ependymocytes, which show expression of CD15 and glutamate aspartate transporter (GLAST) (now known as SLC1A3), that, in addition to astrocytes, have been related to radial glia and stem/precursor cell phenotypes [41]. Additionally, Paniagua-Torija, et al observed that the ependymal region is enriched in cannabinoid receptor type 1 (CB1), which is involved in the regulation of the neural stem [42].…”

“…Additionally, Paniagua-Torija, et al observed that the ependymal region is enriched in cannabinoid receptor type 1 (CB1), which is involved in the regulation of the neural stem [42]. A third feature is the existence of structures previously described as pseudo-canals consisting of cells expressing vimentin and radially oriented around a presumed lumen, which later was discovered to be a blood vessel [41]. Garcia-Ovejero, et al stated that this finding showed the presence of perivascular pseudorosettes, a crucial diagnostic feature for low-grade ependymoma [41-42].…”