Potential of Adult Neural Stem Cells in Stroke Therapy

Andres, Robert H.; Choi, Raymond; Steinberg, Gary K.; Guzman, Raphael

doi:10.2217/17460751.3.6.893

Cited by 45 publications

(38 citation statements)

References 105 publications

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“…post-engraftment NSCs survival is extremely poor, especially in the ischemic core of large infarctions [6] . Endogenous neurogenesis activating after infarction is insufficient to repair the damaged area of brain by itself [7] .…”

Section: Research Articlementioning

confidence: 99%

HIF-1α promotes NSCs migration by modulating Slit2-Robo1 signaling after cerebral ischemia

Ye¹,

Chen²,

2017

Receptor Clin Invest

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Our previous studies have shown that transplantation of Hypoxia-inducible factor-1α (HIF-1α) gene modified neural stem cells (NSCs) reduced brain injury by improving the survival of NSCs and protecting the vascular system. HIF-1α plays pivotal roles during hypoxia, and its downstream pathways might be the primary mechanisms for the growth of NSCs. However, there are very few studies reported whether HIF-1α regulates NSCs migration. In this study, to test the hypothesis that HIF-1α modulates migration of NSCs after cerebral ischemia, we compared the injection of HIF-1α gene recombinant adenovirus, and control adenovirus in ischemia penumbra at 24 h after transient middle cerebral artery occlusion (tMCAO). BrdU labeled NSCs were transplanted in the lateral ventricle at the same time in both groups. The modified neurological severity score (NSS) was used to evaluate neurological deficits. Immunohistochemistry for HIF-1α, BrdU, Slit2 and Robo1 were performed. Comparing with vehicle group HIF-1α group showed better behavioral recovery on day 21 and 28. Expression of HIF-1α in HIF-1α group is higher than that in vehicle group. In HIF-1α group, more BrdU-positive cells were found than that in vehicle group. There are increased Slit2 in HIF-1α group. However, robo1, a receptor of Slits is decreased than that in vehicle group. Thus, we concluded that in cerebral ischemia rat model HIF-1α increased NSCs migration by inhibiting Slit2-Robo1 pathway, and improved the neurological behavior. In conclusion, our results indicate that HIF-1α may be a potential therapeutic target for ischemic stroke through promoting neuroregeneration.

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Section: Research Articlementioning

confidence: 99%

HIF-1α promotes NSCs migration by modulating Slit2-Robo1 signaling after cerebral ischemia

Ye¹,

Chen²,

2017

Receptor Clin Invest

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“…[22][23][24] Further research to determine the optimal cell population and method of administration is needed to improve the outcome of cell therapy for stroke. In addition, the optimal time point of post-ischaemic transplantation has yet to be determined, as activated microglia might limit survival of transplanted cells.…”

Section: Early Clinical Trials For Cell Transplantation With Differenmentioning

confidence: 99%

Progress and prospects: stem cells and neurological diseases

2010

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“…However, NSC survival post-engraftment is generally poor, especially in the ischemic core of large lesions [12]. Olfactory ensheathing cells (OECs), the glia surrounding the primary olfactory neurons throughout their trajectory from the olfactory mucosa to the olfactory bulb glomeruli, possess several attributes that make them particularly interesting in the repair of CNS lesions [13].…”

Section: Introductionmentioning

confidence: 99%

Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat

et al. 2017

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Effects of neural stem cell and olfactory ensheathing cell cotransplants on tissue remodelling after transient focal cerebral ischemia in the adult rat. Neurochemical Research, 42(6), pp. 1599-1609.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/136264/ with the host-tissue post-transplantation is poor. In this study, we address this challenge by testing whether co-grafting of NSCs with olfactory ensheathing cells (OECs), a special type of glia with proven neuroprotective, immunomodulatory, and angiogenic effects, can promote graft survival and host tissue remodelling. Transient focal cerebral ischemia was induced in adult rats by a sixty-minute middle cerebral artery occlusion (MCAo) followed by reperfusion. Ischemic lesions were verified by neurological testing and magnetic resonance imaging (MRI). Transplantation into the globus pallidus of NSCs alone or in combination with OECs was performed at two weeks post-MCAo, followed by histological analyses at three weeks post-transplantation. We found evidence of extensive vascular remodelling in the ischemic core as well as evidence of NSC motility away from the graft and into the infarct border in severely lesioned animals co-grafted with OECs. These findings support a possible role of OECs as part of an in situ tissue engineering paradigm for transplant mediated repair of ischemic brain lesions.

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Potential of Adult Neural Stem Cells in Stroke Therapy

Cited by 45 publications

References 105 publications

HIF-1α promotes NSCs migration by modulating Slit2-Robo1 signaling after cerebral ischemia

HIF-1α promotes NSCs migration by modulating Slit2-Robo1 signaling after cerebral ischemia

Progress and prospects: stem cells and neurological diseases

Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat

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