Adult human spinal cord harbors neural precursor cells that generate neurons and glial cells in vitro

Abstract

Adult human and rodent brains contain neural stem and progenitor cells, and the presence of neural stem cells in the adult rodent spinal cord has also been described. Here, using electron microscopy, expression of neural precursor cell markers, and cell culture, we investigated whether neural precursor cells are also present in adult human spinal cord. In well-preserved nonpathological post-mortem human adult spinal cord, nestin, Sox2, GFAP, CD15, Nkx6.1, and PSA-NCAM were found to be expressed heterogeneously by cells located around the central canal. Ultrastructural analysis revealed the existence of immature cells close to the ependymal cells, which display characteristics of type B and C cells found in the adult rodent brain subventricular region, which are considered to be stem and progenitor cells, respectively. Completely dissociated spinal cord cells reproducibly formed Sox2(+) nestin(+) neurospheres containing proliferative precursor cells. On differentiation, these generate glial cells and gamma-aminobutyric acid (GABA)-ergic neurons. These results provide the first evidence for the existence in the adult human spinal cord of neural precursors with the potential to differentiate into neurons and glia. They represent a major interest for endogenous regeneration of spinal cord after trauma and in degenerative diseases.

The Spinal Cord Neural Stem Cell Niche

“…First, in contrast to mice, the central canal of the human spinal cord is often occluded (Dromard et al 2008), as previously reported by (Fuller and Burger 1997;Milhorat, Kotzen, and Anzil 1994), and the ependymal region appeared disorganized, with the frequent presence of rosettes or microcanals. Reminiscent of the reported difference between the SVZ in rodents and humans (Quinones-Hinojosa et al 2006), the human central canal is surrounded by a hypocellular region containing a high density of GFAP filaments and nerve fibers (Dromard et al 2008). Equally contrasting with rodents, a cluster of Nestin + subependymal cells was repeatedly observed in the ventral regions of cervical and lumbar spinal cords.…”

“…There are major differences between the rodent and primate brain, not only concerning size and organization but also for the cell diversity and SVZ organization. Consequently, we set out to explore the organization of the central canal region and the presence of neural stem cells in the adult human spinal cord (Dromard et al 2008). For this purpose, we used lumbar spinal cords from brain-dead organ-donor patients (24-70 years old) (Fig.…”

Nestin-Positive Ependymal Cells Are Increased in the Human Spinal Cord after Traumatic Central Nervous System Injury

“…Cells removed from the ependymal regions of spinal cords from fresh autopsy tissue (organ transplant donors) differentiated into neurons and glia in vitro, 17,18 suggesting both a multipotent and a self-renewing capacity. Neurospheres formed from these cells expressed high levels of nestin, a marker of neural progenitor cells, and SOX2, a marker of neural stem cells, and displayed a morphology with long nestin-positive processes radially emanating from the neurospheres 18 in a manner reminiscent of tanycyte morphology.…”

“…11,14,16 Endogenous NPC present in the adult human spinal cord have been isolated from fresh autopsy tissue, cultured, and shown to differentiate into neurons and glial cells in vitro. 17,18 One of the common markers for progenitor cells, nestin, is increased in the ependyma of human spinal cords from patients with multiple sclerosis, 19 amyotrophic lateral sclerosis (ALS), and spinal tumors, 20 and in hydrocephalic infants. 21 There are discrepancies in the reported antigenicity, development, location, and response of cells purported to be NPC in the spinal cord injury.…”

“…AlfaroCervello and associates 22 described biciliated ependymal cells of the central canal that are nestin positive and glial fibrillary acid protein (GFAP) negative, and which proliferate slowly under normal growth conditions. Dromard and associates 17 indicated a cluster of nestin-positive cells located in the ventral subependymal region as being a possible neurogenic niche, whereas Hamilton and associates 8 reported that cells with stem cell characteristics may be located in the dorsal pole of the central canal and have a tanycytelike morphology. Rat tanycytes in the ependyma lining the cerebral ventricles and spinal cord have been described in detail, [23][24][25] and although they have little regenerative capacity, they do respond to injury and have a stronger response in the spinal cord than in the brain.…”