Transplanted adult spinal cord–derived neural stem/progenitor cells promote early functional recovery after rat spinal cord injury

Parr, Ann M.; Kulbatski, Iris; Zahir, Tasneem; Wang, X.; Yue, Chun; Keating, Armand; Tator, Charles H.

doi:10.1016/j.neuroscience.2008.05.042

Cited by 168 publications

(136 citation statements)

References 45 publications

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“…This is consistent with our earlier studies in which NSPC transplanted directly into the cord after impact-compression injury 13 or into focal demyelination lesions induced by ethidium bromide 12 differentiated primarily into oligodendrocytes. LP transplanted NSPC did not express neuronal markers.…”

Section: Resultssupporting

confidence: 93%

“…12 We have also shown a neuroprotective function of spinal cord NSPC after subacute transplantation directly into the injured rat spinal cord. 13 The purpose of the present study was to examine the distribution and phenotype of adult rat spinal cord-derived NSPC following LP transplantation into the injured rat spinal cord. We also examined LP transplantation of rat BMSC, which have been shown to home to sites of injury.…”

Section: Introductionmentioning

confidence: 99%

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Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat

et al. 2011

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Study design: Experimental investigation of intrathecal transplantation of stem cells by lumbar puncture (LP) in a rat model that simulates human thoracic spinal cord injury (SCI). Objectives: To examine the distribution and phenotype of spinal cord-derived neural stem/progenitor cells (NSPCs) and bone marrow-derived mesenchymal stromal cells (BMSCs) following LP transplantation in SCI rats. Setting: Toronto Western Research Institute, Toronto, Ontario, Canada. Methods: NSPCs or BMSCs were transplanted via LP at level L3-5 1 week after compression SCI at T8. Rats were killed at 3, 17 and 27 days after LP transplantation and the relative distribution of cells at C4, T8 and L3-5 was quantitated. The phenotype of the NSPC and BMSC was assessed with immunocytochemistry in vitro and following LP transplantation. Results: By 4 weeks, more NSPC migrated to the lesion site relative to BMSC and uninjured animals. However, there was no preferential homing of either of these types of cells into the parenchyma of the injury site, and most of the transplanted cells remained in the intrathecal space. In vitro, spinal cord-derived NSPC proliferated and expressed nestin, but after LP transplantation, NSPC became post-mitotic and primarily expressed oligodendrocyte markers. In contrast, BMSC did not express any neural antigens in vivo. Conclusion: LP is a minimally invasive method of cell transplantation that produces wide dissemination of cells in the subarachnoid space of the spinal cord. This is the first study to report and quantify the phenotype and spatial distribution of LP transplanted NSPC and BMSC in the intact and injured spinal cord.

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Section: Resultssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat

et al. 2011

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“…2006;Parr et al, , 2008Pfeifer et al, 2004;; expression of neuronal markers was generally rare (0-1%). The extent to which these oligodendrocytes can mature in the injured spinal cord and generate compact myelin is inconsistently reported (Karimi-Abdolrezaee et al, 2006;Parr et al, 2008). Six of the eight contusion studies evaluated behavioral recovery with open field BBB locomotor scores.…”

Section: Neural Stem=progenitor Cells From Embryonic Stem Cellsmentioning

confidence: 99%

“…Six of the eight contusion studies evaluated behavioral recovery with open field BBB locomotor scores. Five of these six studies reported significant improvement with the transplantation of aNPCs, three in rats (Hofstetter et al, 2005;Karimi-Abdolrezaee et al, 2006;Parr et al, 2008) and two in mice (Bottai et al, 2008;Ziv et al, 2006). However, it needs to be pointed out that in some of these studies, co-treatments were also applied, such as myelin vaccination (Ziv et al, 2006) or a cocktail of trophic factors infused intrathecally for 1 week (Karimi-Abdolrezaee et al, 2006).…”

Section: Neural Stem=progenitor Cells From Embryonic Stem Cellsmentioning

confidence: 99%

A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury

Tetzlaff

Okon

Karimi-Abdolrezaee

et al. 2011

Journal of Neurotrauma

496

463

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Cell transplantation therapies have become a major focus in pre-clinical research as a promising strategy for the treatment of spinal cord injury (SCI). In this article, we systematically review the available pre-clinical literature on the most commonly used cell types in order to assess the body of evidence that may support their translation to human SCI patients. These cell types include Schwann cells, olfactory ensheathing glial cells, embryonic and adult neural stem=progenitor cells, fate-restricted neural=glial precursor cells, and bone-marrow stromal cells. Studies were included for review only if they described the transplantation of the cell substrate into an in-vivo model of traumatic SCI, induced either bluntly or sharply. Using these inclusion criteria, 162 studies were identified and reviewed in detail, emphasizing their behavioral effects (although not limiting the scope of the discussion to behavioral effects alone). Significant differences between cells of the same ''type'' exist based on the species and age of donor, as well as culture conditions and mode of delivery. Many of these studies used cell transplantations in combination with other strategies. The systematic review makes it very apparent that cells derived from rodent sources have been the most extensively studied, while only 19 studies reported the transplantation of human cells, nine of which utilized bone-marrow stromal cells. Similarly, the vast majority of studies have been conducted in rodent models of injury, and few studies have investigated cell transplantation in larger mammals or primates. With respect to the timing of intervention, nearly all of the studies reviewed were conducted with transplantations occurring subacutely and acutely, while chronic treatments were rare and often failed to yield functional benefits.

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“…In support of this viewpoint, coculture experiments have shown that ECs increase proliferation of NSPCs derived from the adult SVZ, thereby promoting neurogenesis [6,7]. However, accumulating evidence indicates that NSPCs are present in many parts of the adult brain, including the cortex [8][9][10], subcortical white matter [11], and spinal cord [12][13][14]; that is, outside conventional neurogenic zones, including SVZ and SGZ. Recently, we also found that NSPCs developed in the poststroke area of the cortex in the adult murine brain (ischemia-induced NSPCs) [8], and that ECs promoted the proliferation of these NSPCs, thereby enhancing neurogenesis after ischemia [15].…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow Mononuclear Cells Promote Proliferation of Endogenous Neural Stem Cells Through Vascular Niches After Cerebral Infarction

et al. 2010

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Increasing evidence shows that administration of bone marrow mononuclear cells (BMMCs) is a potential treatment for various ischemic diseases, such as ischemic stroke. Although angiogenesis has been considered primarily responsible for the effect of BMMCs, their direct contribution to endothelial cells (ECs) by being a functional elements of vascular niches for neural stem/progenitor cells (NSPCs) has not been considered. Herein, we examine whether BMMCs affected the properties of ECs and NSPCs, and whether they promoted neurogenesis and functional recovery after stroke. We compared i.v. transplantations 1 3 10 6 BMMCs and phosphate-buffered saline in mice 2 days after cortical infarction. Systemically administered BMMCs preferentially accumulated at the postischemic cortex and periinfarct area in brains; cell proliferation of ECs (angiogenesis) at these regions was significantly increased in BMMCstreated mice compared with controls. We also found that endogenous NSPCs developed in close proximity to ECs in and around the poststroke cortex and that ECs were essential for proliferation of these ischemia-induced NSPCs. Furthermore, BMMCs enhanced proliferation of NSPCs as well as ECs. Proliferation of NSPCs was suppressed by additional treatment with endostatin (known to inhibit proliferation of ECs) following BMMCs transplantation. Subsequently, neurogenesis and functional recovery were also promoted in BMMCs-treated mice compared with controls. These results suggest that BMMCs can contribute to the proliferation of endogenous ischemia-induced NSPCs through vascular niche regulation, which includes regulation of endothelial proliferation. In addition, these results suggest that BMMCs transplantation has potential as a novel therapeutic option in stroke treatment.

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Transplanted adult spinal cord–derived neural stem/progenitor cells promote early functional recovery after rat spinal cord injury

Cited by 168 publications

References 45 publications

Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat

Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat

A Systematic Review of Cellular Transplantation Therapies for Spinal Cord Injury

Bone Marrow Mononuclear Cells Promote Proliferation of Endogenous Neural Stem Cells Through Vascular Niches After Cerebral Infarction

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