Intracerebral transplantation of foetal neural stem cells improves brain dysfunction induced by intracerebral haemorrhage stroke in mice

Wang, Zhenzhong; Cui, Chuang; Li, Qiulin; Zhou, Shiyue; Jia-feng, FU; Wang, Xiangdong; Zhuge, Qichuan

doi:10.1111/j.1582-4934.2011.01259.x

Cited by 21 publications

(21 citation statements)

References 35 publications

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“…While there have been previous reports using NSC transplantation in ICH, most of these studies transplanted cells at later time points to study their effects on functional recovery. 5,6,8 In our study, we focused on the effects of transplants during the acute stage to examine the ability of these cells to survive during this critical period, as well as the potential for neuroprotection.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown the neuroprotection of intraparenchymal cell transplants that can ameliorate primary and secondary injury in animals with ICH, as well as enhance functional recovery. [5][6][7][8][9][10][11][12] At the site of neuroprotection, the transplantation should be performed at the acute stage of ICH, because the irreversible brain damage extends as time goes by. However, the hostile host environment during the acute stage of ICH limits the efficacy of this strategy as more than 85% of transplanted cells are no longer present 8 weeks after transplant.…”

Section: Introductionmentioning

confidence: 99%

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Hypoxic preconditioning enhances neural stem cell transplantation therapy after intracerebral hemorrhage in mice

Wakai

Narasimhan

Sakata

et al. 2016

J Cereb Blood Flow Metab

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Previous studies have shown that intraparenchymal transplantation of neural stem cells ameliorates neurological deficits in animals with intracerebral hemorrhage. However, hemoglobin in the host brain environment causes massive grafted cell death and reduces the effectiveness of this approach. Several studies have shown that preconditioning induced by sublethal hypoxia can markedly improve the tolerance of treated subjects to more severe insults. Therefore, we investigated whether hypoxic preconditioning enhances neural stem cell resilience to the hemorrhagic stroke environment and improves therapeutic effects in mice. To assess whether hypoxic preconditioning enhances neural stem cell survival when exposed to hemoglobin, neural stem cells were exposed to 5% hypoxia for 24 hours before exposure to hemoglobin. To study the effectiveness of hypoxic preconditioning on grafted-neural stem cell recovery, neural stem cells subjected to hypoxic preconditioning were grafted into the parenchyma 3 days after intracerebral hemorrhage. Hypoxic preconditioning significantly enhanced viability of the neural stem cells exposed to hemoglobin and increased grafted-cell survival in the intracerebral hemorrhage brain. Hypoxic preconditioning also increased neural stem cell secretion of vascular endothelial growth factor. Finally, transplanted neural stem cells with hypoxic preconditioning exhibited enhanced tissue-protective capability that accelerated behavioral recovery. Our results suggest that hypoxic preconditioning in neural stem cells improves efficacy of stem cell therapy for intracerebral hemorrhage.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypoxic preconditioning enhances neural stem cell transplantation therapy after intracerebral hemorrhage in mice

Wakai

Narasimhan

Sakata

et al. 2016

J Cereb Blood Flow Metab

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“…Many stem cell administration routes have been tested, but it remains unclear which is the best option. Findings in ICH model support that cervical vein delivery is inefficient [133] , whereas good outcomes were already observed following stem cell delivery in brain parenchyma [66,111,[113][114][115][116]121,126,[134][135][136][137] , lateral ventricle [120,133] , tail vein [117,119,122,[124][125][126]138,139] , and carotid artery [133,140,141] . However, each one of these alternatives has drawbacks.…”

Section: Preclinical Studies: An Heterogeneous Approach For An Heteromentioning

confidence: 70%

“…; 1 × 10 6 1000; 2000 TV Vaquero et al [136] Col Ⅳ hBMSC [119] Col Ⅶ BMSC 1 h 1 × 10 6 1000 TV Wang et al [137] Col Ⅶ NSC 72 h 1 × 10 6 500 (TV); 2 (BP) TV; BP Yang et al [121] Col Ⅰ BMSC (overexpressing GDNF) 72 h 5 × 10 5 20 BP Yang et al [117] ABI hUCSC 24 h; 72 h; 7 d 3 × 10 6 2000 TV Yang et al [159] Col Ⅶ hASC 24 h 1 × 10 6 200 FV Zhang et al [133] Col Ⅶ …”

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confidence: 99%

Stem cell therapy in intracerebral hemorrhage rat model

Cordeiro

Horn

2015

WJSC

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Intracerebral hemorrhage (ICH) is a very complex pathology, with many different not fully elucidated etiologies and prognostics. It is the most severe subtype of stroke, with high mortality and morbidity rates. Unfortunately, despite the numerous promising preclinical assays including neuroprotective, anti-hypertensive, and anti-inflammatory drugs, to this moment only symptomatic treatments are available, motivating the search for new alternatives. In this context, stem cell therapy emerged as a promising tool. However, more than a decade has passed, and there is still much to be learned not only about stem cells, but also about ICH itself, and how these two pieces come together. To date, rats have been the most widely used animal model in this research field, and there is much more to be learned from and about them. In this review, we first summarize ICH epidemiology, risk factors, and pathophysiology. We then present different methods utilized to induce ICH in rats, and examine how accurately they represent the human disease. Next, we discuss the different types of stem cells used in previous ICH studies, also taking into account the tested transplantation sites. Finally, we summarize what has been achieved in assays with stem cells in rat models of ICH, and point out some relevant issues where attention must be given in future efforts. Core tip: In this review, we first summarize intracerebral hemorrhage (ICH) epidemiology, risk factors, and pathophysiology. We then present different methods utilized to induce ICH in rats, and examine how accurately they represent the human disease. Next, we discuss the different types of stem cells used in previous ICH studies, also taking into account the tested transplantation sites. Finally, we summarize what has been achieved in assays with stem cells in rat models of ICH, and point out some relevant issues where attention must be given in future efforts.Cordeiro MF, Horn AP. Stem cell therapy in intracerebral hemorrhage rat model. World J Stem Cells 2015; 7(3): 618-629

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“…5,6,8,38 The present SOD1 enhances stem cell therapy in mouse ICH T Wakai et al study shows that transplantation of SOD1 Tg NSCs in ICH brains reduced their atrophy and death. Moreover, an improvement in the outcome of behavioral tests was observed in these animals, indicating that stem cells facilitate neuroprotection after being grafted to ICH brains.…”

Section: Discussionmentioning

confidence: 86%

Transplantation of Neural Stem Cells That Overexpress Sod1 Enhances Amelioration of Intracerebral Hemorrhage in Mice

Wakai

Sakata

Narasimhan

et al. 2013

J Cereb Blood Flow Metab

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Previous studies have shown that intraparenchymal transplantation of neural stem cells (NSCs) ameliorates neurologic deficits in animals with intracerebral hemorrhage (ICH). However, massive grafted cell death after transplantation, possibly caused by a hostile host brain environment, lessens the effectiveness of this approach. We focused on the effect of oxidative stress against grafted NSCs and hypothesized that conferring antioxidant properties to transplanted NSCs may overcome their death and enhance neuroprotection after ICH. Copper/zinc-superoxide dismutase (SOD1) is a specific antioxidant enzyme that counteracts superoxide anions. We investigated whether genetic manipulation to overexpress SOD1 enhances survival of grafted NSCs and accelerates amelioration of ICH. Neural stem cells that overexpress SOD1 were administered intracerebrally 3 days after ICH in a mouse model. Histologic and behavioral tests were examined after ICH. Copper/zinc-superoxide dismutase overexpression protected the grafted NSCs via a decrease in production of reactive oxygen species. This resulted in an increase in paracrine factors released by the NSCs, and an increase in surviving neurons in the striatum and a reduction in striatal atrophy. In addition, SOD1 overexpression showed progressive improvement in behavioral recovery. Our results suggest that enhanced antioxidative activity in NSCs improves efficacy of stem cell therapy for ICH.

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Intracerebral transplantation of foetal neural stem cells improves brain dysfunction induced by intracerebral haemorrhage stroke in mice

Cited by 21 publications

References 35 publications

Hypoxic preconditioning enhances neural stem cell transplantation therapy after intracerebral hemorrhage in mice

Hypoxic preconditioning enhances neural stem cell transplantation therapy after intracerebral hemorrhage in mice

Stem cell therapy in intracerebral hemorrhage rat model

Transplantation of Neural Stem Cells That Overexpress Sod1 Enhances Amelioration of Intracerebral Hemorrhage in Mice

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