Origin of New Glial Cells in Intact and Injured Adult Spinal Cord

Barnabé-Heider, Fanie; Göritz, Christian; Sabelström, Hanna; Takebayashi, Hirohide; Pfrieger, Frank W.; Meletis, Konstantinos; Frisén, Jonas

doi:10.1016/j.stem.2010.07.014

Cited by 534 publications

(721 citation statements)

References 56 publications

(94 reference statements)

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“…12 Dividing cells express markers of mature astrocytes or oligodendrocytes, but remain in situ rather than migrating to the surrounding tissue. 13 After spinal cord injury in the rat, NPCs proliferate and differentiate into glial cells but not neurons, 5,14,15 and can migrate toward an injury site. 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.…”

Section: Introductionmentioning

confidence: 99%

“…13 After spinal cord injury in the rat, NPCs proliferate and differentiate into glial cells but not neurons, 5,14,15 and can migrate toward an injury site. 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.…”

Section: Introductionmentioning

confidence: 99%

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

Cawsey

Duflou

Weickert

et al. 2015

Journal of Neurotrauma

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Endogenous neural progenitor cell niches have been identified in adult mammalian brain and spinal cord. Few studies have examined human spinal cord tissue for a neural progenitor cell response in disease or after injury. Here, we have compared cervical spinal cord sections from 14 individuals who died as a result of nontraumatic causes (controls) with 27 who died from injury with evidence of trauma to the central nervous system. Nestin immunoreactivity was used as a marker of neural progenitor cell response. There were significant increases in the percentage of ependymal cells that were nestin positive between controls and trauma cases. When sections from lumbar and thoracic spinal cord were available, nestin positivity was seen at all three spinal levels, suggesting that nestin reactivity is not simply a localized reaction to injury. There was a positive correlation between the percentage of ependymal cells that were nestin positive and post-injury survival time but not for age, postmortem delay, or glial fibrillary acidic protein (GFAP) immunoreactivity. No doublelabelled nestin and GFAP cells were identified in the ependymal, subependymal, or parenchymal regions of the spinal cord. We need to further characterize this subset of ependymal cells to determine their role after injury, whether they are a population of neural progenitor cells with the potential for proliferation, migration, and differentiation for spinal cord repair, or whether they have other roles more in line with hypothalamic tanycytes, which they closely resemble.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Cawsey

Duflou

Weickert

et al. 2015

Journal of Neurotrauma

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“…Following spinal cord injury (SCI), a cascade of pathological processes occurs, including the breaking down of the vasculature system, edema, infiltration of immune cells, inflammation, initiation of wound healing processes, seizing of ongoing neurotransmission, gliosis/glial scar formation, cell death, demyelination, and remyelination (7), along with activation of neural stem/ progenitor cells (NPCs) attempting to participate in neural repair (8). Often, prolonged activation of immune cells, including microglia, lymphocytes, and macrophages, leads to secondary lesions of the nervous system, creating a very harsh environment for already compromised CNS neurons to regenerate axons (9).…”

mentioning

confidence: 99%

“…It has been widely accepted that neural stem cells (NSCs) reside in many regions of the adult CNS (8,12,13). CNS injury frequently causes neuronal loss.…”

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confidence: 99%

NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury

Yang

Zhang

Duan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

171

172

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Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury.spinal cord injury | NT3 | chitosan | functional recovery | endogenous neurogenesis

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“…Recent work by Sellers et al [68] demonstrated differential cell fate of NG2 cells after SCI; NG2 cells generated 24 h after injury gave rise to astrocytes, whereas those generated 1 week postinjury produced OLs. However, more recent data using lineage tracing following SCI call the ability of OPCs to give rise to astrocytes after SCI into question [69]. Direct evidence that NG2 cells contribute to replacement of mature OLs after SCI was recently provided using the CNP-EGFP (2',3'-Cyclic-nucleotide 3'-phosphodiesterase gene-enhanced green fluorescent protein) mouse to definitively show that EGFP + NG2 + cells differentiate into OLs after SCI [70].…”

Section: Replacement Of Ols By Endogenous Progenitors After Scimentioning

confidence: 99%

Oligodendrocyte Fate after Spinal Cord Injury

2011

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Summary: Oligodendrocytes (OLs) are particularly susceptible to the toxicity of the acute lesion environment after spinal cord injury (SCI). They undergo both necrosis and apoptosis acutely, with apoptosis continuing at chronic time points. Loss of OLs causes demyelination and impairs axon function and survival. In parallel, a rapid and protracted OL progenitor cell proliferative response occurs, especially at the lesion borders. Proliferating and migrating OL progenitor cells differentiate into myelinating OLs, which remyelinate demyelinated axons starting at 2 weeks postinjury. The progression of OL lineage cells into mature OLs in the adult after injury recapitulates development to some degree, owing to the plethora of factors within the injury milieu. Although robust, this endogenous oligogenic response is insufficient against OL loss and demyelination. First, in this review we analyze the major spatial-temporal mechanisms of OL loss, replacement, and myelination, with the purpose of highlighting potential areas of intervention after SCI. We then discuss studies on OL protection and replacement. Growth factors have been used both to boost the endogenous progenitor response, and in conjunction with progenitor transplantation to facilitate survival and OL fate. Considerable progress has been made with embryonic stem cellderived cells and adult neural progenitor cells. For therapies targeting oligogenesis to be successful, endogenous responses and the effects of the acute and chronic lesion environment on OL lineage cells must be understood in detail, and in relation, the optimal therapeutic window for such strategies must also be determined.

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Origin of New Glial Cells in Intact and Injured Adult Spinal Cord

Cited by 534 publications

References 56 publications

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

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

NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury

Oligodendrocyte Fate after Spinal Cord Injury

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