Targeting ependymal stem cells in vivo as a non-invasive therapy for spinal cord injury

Barreiro‐Iglesias, Antón

doi:10.1242/dmm.006643

Cited by 12 publications

(14 citation statements)

References 16 publications

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“…The majority of research regarding NPCs has been performed in rodent models. Most of these studies have found NPCs to generate a majority of cells with an astrocytic phenotype and some oligodendrocytes and OPC, similar to the behavior of transplanted cells (Barreiro-Iglesias, 2010). A proliferative burst occurring in CNS-derived progenitors as early as 24 h post-SCI has been demonstrated however the cells differentiated along glial lines with no evidence of neural differentiation (Horky et al, 2006).…”

Section: Introductionmentioning

confidence: 76%

Differences in the Cellular Response to Acute Spinal Cord Injury between Developing and Mature Rats Highlights the Potential Significance of the Inflammatory Response

Sutherland

Mathews

Mao

et al. 2017

Front. Cell. Neurosci.

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There exists a trend for a better functional recovery from spinal cord injury (SCI) in younger patients compared to adults, which is also reported for animal studies; however, the reasons for this are yet to be elucidated. The post injury tissue microenvironment is a complex milieu of cells and signals that interact on multiple levels. Inflammation has been shown to play a significant role in this post injury microenvironment. Endogenous neural progenitor cells (NPC), in the ependymal layer of the central canal, have also been shown to respond and migrate to the lesion site. This study used a mild contusion injury model to compare adult (9 week), juvenile (5 week) and infant (P7) Sprague-Dawley rats at 24 h, 1, 2, and 6 weeks post-injury (n = 108). The innate cells of the inflammatory response were examined using counts of ED1/IBA1 labeled cells. This found a decreased inflammatory response in the infants, compared to the adult and juvenile animals, demonstrated by a decreased neutrophil infiltration and macrophage and microglial activation at all 4 time points. Two other prominent cellular contributors to the post-injury microenvironment, the reactive astrocytes, which eventually form the glial scar, and the NPC were quantitated using GFAP and Nestin immunohistochemistry. After SCI in all 3 ages there was an obvious increase in Nestin staining in the ependymal layer, with long basal processes extending into the parenchyma. This was consistent between age groups early post injury then deviated at 2 weeks. The GFAP results also showed stark differences between the mature and infant animals. These results point to significant differences in the inflammatory response between infants and adults that may contribute to the better recovery indicated by other researchers, as well as differences in the overall injury progression and cellular responses. This may have important consequences if we are able to mirror and manipulate this response in patients of all ages; however much greater exploration in this area is required.

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Section: Introductionmentioning

confidence: 76%

Differences in the Cellular Response to Acute Spinal Cord Injury between Developing and Mature Rats Highlights the Potential Significance of the Inflammatory Response

Sutherland

Mathews

Mao

et al. 2017

Front. Cell. Neurosci.

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“…Many studies have shown the Olig family (particularly Olig1 and Olig2 members), promotes restoration of the demyelinated central nervous system and may contribute to neural regeneration[4539]. Additionally, many studies have closely examined the relationship between Olig2 alone, and central nervous system gliomas[404142].…”

Section: The Olig Famliy In Central Nervous Diseasementioning

confidence: 99%

“…Endogenous neural stem cells in the central nervous system are activated to generate more daughter cells in response to injury, but barely cause recovery, suggesting that it is not enough to recruit and activate these stem cells[5]. …”

Section: The Olig Famliy In Central Nervous Diseasementioning

confidence: 99%

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The Olig family affects central nervous system development and disease

Tan

Yin

et al. 2014

Neural Regen Res

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Neural cell differentiation and maturation is a critical step during central nervous system development. The oligodendrocyte transcription family (Olig family) is known to be an important factor in regulating neural cell differentiation. Because of this, the Olig family also affects acute and chronic central nervous system diseases, including brain injury, multiple sclerosis, and even gliomas. Improved understanding about the functions of the Olig family in central nervous system development and disease will greatly aid novel breakthroughs in central nervous system diseases. This review investigates the role of the Olig family in central nervous system development and related diseases.

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“…Therefore, it is of great importance to follow different lines of research to increase our knowledge of this condition and to develop new therapies. In contrast to mammals, lampreys and fishes are capable of repairing their spinal cord and regaining locomotion after a complete SCI [1][2][3][4]. In the last decade, zebrafish has appeared as a very valuable genetically tractable model that can be used to understand the mechanisms that control successful spinal cord regeneration in aquatic animals.…”

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confidence: 99%

Transgenic Zebrafish Lines as Valuable Tools to Understand Successful Spinal Cord Regeneration

Barreiro‐Iglesias¹

2013

Clon Transgen

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Spinal cord injury (SCI) is a devastating condition that in humans leads to permanent disability. Currently, there is not yet a satisfactory treatment to cure and completely repair the damaged spinal cord in humans. Therefore, it is of great importance to follow different lines of research to increase our knowledge of this condition and to develop new therapies. In contrast to mammals, lampreys and fishes are capable of repairing their spinal cord and regaining locomotion after a complete SCI [1][2][3][4]. In the last decade, zebrafish has appeared as a very valuable genetically tractable model that can be used to understand the mechanisms that control successful spinal cord regeneration in aquatic animals. Lampreys and other species of teleost fishes are being mainly used for this type of studies [lampreys: [5][6][7][8]; teleosts: [9,10]. For example, studies performed using the lamprey model of SCI have shown that different reticulospinal descending neurons projecting in a similar region of the spinal cord have different regenerative abilities after axotomy [4,5] even in the presence of functional recovery. Recent findings using lampreys have also shown that those brain neurons that are "bad regenerators" usually die after a complete spinal cord transaction [3,5]. Other studies in lampreys have suggested that changes in the expression of axonal guidance molecules or neurotransmitter receptors could be responsible for the success/failure of the regeneration process after injury [11][12][13]. These and other studies have shown that lampreys are great models to study successful spinal cord regeneration. However, lampreys have a very long and complex life cycle (approximately 9 years long) involving a metamorphosis process, which makes them not suitable to generate transgenic or mutant lines that would facilitate to design and perform more functional studies.On the other hand, zebrafish is an animal model with a short life cycle, which has facilitated greatly the generation of different transgenic and mutant lines. Transgenic and mutant animals can be used to understand the molecular mechanisms that lead to successful regeneration of the spinal cord in fishes. Recent studies using transgenic mice have shown that new cells are produced in the mammalian spinal cord after injury, although only glial cells are generated [14,15]. We could translate the knowledge acquired in zebrafish studies to design new therapies to promote neuronal and axonal regeneration in mammals including humans. For example, Dias and co-workers [16] have recently used a double-transgenic zebrafish line [Tg(hsp70l:Gal4)×Tg(UAS:myc-notch1a-intra)], in which a heatshock promoter drives expression of the active intracellular domain of notch1a, to show that Notch signalling controls the generation of new motor neurons after SCI in adult zebrafish. Also, a transgenic zebrafish line, Tg(shha:GFP), has been used as a sonic hedgehog reporter line to show that hedgehog signalling is involved in the generation of new serotonergic interneurons after SCI in...

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Targeting ependymal stem cells in vivo as a non-invasive therapy for spinal cord injury

Cited by 12 publications

References 16 publications

Differences in the Cellular Response to Acute Spinal Cord Injury between Developing and Mature Rats Highlights the Potential Significance of the Inflammatory Response

Differences in the Cellular Response to Acute Spinal Cord Injury between Developing and Mature Rats Highlights the Potential Significance of the Inflammatory Response

The Olig family affects central nervous system development and disease

Transgenic Zebrafish Lines as Valuable Tools to Understand Successful Spinal Cord Regeneration

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