title: 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.
authors.affiliation: 1 Laboratory of Neuroinflammation, Hospital Nacional de Paraplejicos (SESCAM), Toledo, Spain dgarciao@sescam.jccm.es.
authors.forename: Daniel
authors.initials: D
authors.lastname: Garcia-Ovejero
authors.affiliation: 1 Laboratory of Neuroinflammation, Hospital Nacional de Paraplejicos (SESCAM), Toledo, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Arevalo-Martin
authors.affiliation: 1 Laboratory of Neuroinflammation, Hospital Nacional de Paraplejicos (SESCAM), Toledo, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Paniagua-Torija
authors.affiliation: 2 Radiology Unit, Hospital Nacional de Paraplejicos (SESCAM), Toledo, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Florensa-Vila
authors.affiliation: 3 Institut de Neuropatologia, Servei d'Anatomia Patolo`gica, IDIBELL-Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain.
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.affiliation: 4 Center for Spinal Cord Injuries, Trauma Center Murnau, Germany 5 Institute of Molecular Regenerative Medicine, SCI-TReCS (Spinal Cord Injury and Tissue Regeneration Center Salzburg), Paracelsus Medical University, Salzburg, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Grassner
authors.affiliation: 1 Laboratory of Neuroinflammation, Hospital Nacional de Paraplejicos (SESCAM), Toledo, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Molina-Holgado
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology; D016022:Case-Control Studies; D004805:Ependyma / Q000033:anatomy & histology* / Q000378:metabolism / Q000473:pathology; D004806:Ependymoma / Q000235:genetics / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D013045:Species Specificity; D013115:Spinal Canal / Q000033:anatomy & histology / Q000473:pathology; D013116:Spinal Cord / Q000033:anatomy & histology* / Q000378:metabolism / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000473:pathology; D013120:Spinal Cord Neoplasms / Q000473:pathology*; D055815:Young Adult
keywords: central canal; ependymoma; neural stem cells; regeneration; spinal cord injury