Transplantation of neural stem cells expressing hypoxia-inducible factor-1α (HIF-1α) improves behavioral recovery in a rat stroke model

Wu, Weiqiang; Chen, Xiu; Chang-lin, HU; Li, Jinfang; Yu, Zhe; Cai, Wenqin

doi:10.1016/j.jocn.2009.03.039

Cited by 56 publications

(56 citation statements)

References 30 publications

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“…Up to date, various stem cell delivery routes such as intravenous, intracerebral, intraartery, and intraventricular have been applied to explore their therapeutic benefits and the mechanism involved in stroke. 27 Intracerebral injection was chosen in our experimental design because the cells could be precisely transplanted into the striatum of ischemic brain without cell loss. Vascular injection could trap stem cells into systemic organs, with few stem cells could be homed to the ischemic brain hemisphere.…”

Section: Discussionmentioning

confidence: 99%

Neural Stem Cell Protects Aged Rat Brain from Ischemia–Reperfusion Injury through Neurogenesis and Angiogenesis

Tang

Wang

Lin

et al. 2014

J Cereb Blood Flow Metab

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Neural stem cells (NSCs) show therapeutic potential for ischemia in young-adult animals. However, the effect of aging on NSC therapy is largely unknown. In this work, NSCs were transplanted into aged (24-month-old) and young-adult (3-month-old) rats at 1 day after stroke. Infarct volume and neurobehavioral outcomes were examined. The number of differentiated NSCs was compared in aged and young-adult ischemic rats and angiogenesis and neurogenesis were also determined. We found that aged rats developed larger infarcts than young-adult rats after ischemia (Po0.05). The neurobehavioral outcome was also worse for aged rats comparing with young-adult rats. Brain infarction and neurologic deficits were attenuated after NSC transplantation in both aged and young-adult rats. The number of survived NSCs in aged rats was similar to that of the young-adult rats (P40.05) and most of them were differentiated into glial fibrillary acidic protein þ (GFAP þ ) cells. More importantly, angiogenesis and neurogenesis were greatly enhanced in both aged and young-adult rats after transplantation compared with phosphate-buffered saline (PBS) control (Po0.05), accompanied by increased expression of vascular endothelial growth factor (VEGF). Our results showed that NSC therapy reduced ischemic brain injury, along with increased angiogenesis and neurogenesis in aged rats, suggesting that aging-related microenvironment does not preclude a beneficial response to NSCs transplantation during cerebral ischemia.

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Section: Discussionmentioning

confidence: 99%

Neural Stem Cell Protects Aged Rat Brain from Ischemia–Reperfusion Injury through Neurogenesis and Angiogenesis

Tang

Wang

Lin

et al. 2014

J Cereb Blood Flow Metab

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“…Transplantation of GDNFtransfected NPCs not only improves functional outcomes, but also increases BDNF expression, ultimately leading to improved cell survival [148] . Hypoxia-induction factor (HIF)-transfected cells were shown to improve functional outcomes, and increase the proliferation of endothelial cells, suggesting increased angiogenesis [149] . These results prompt further study of HIF, especially given HIF's role in inducing the expression of various previously discussed factors, including VEGF, EPO, and HB-EGF.…”

Section: Combinatorial Aproaches To Enhance Stroke Recoverymentioning

confidence: 99%

Role of neural precursor cells in promoting repair following stroke

Dibajnia

Morshead

2012

Acta Pharmacol Sin

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Stem cell-based therapies for the treatment of stroke have received considerable attention. Two broad approaches to stem cell-based therapies have been taken: the transplantation of exogenous stem cells, and the activation of endogenous neural stem and progenitor cells (together termed neural precursors). Studies examining the transplantation of exogenous cells have demonstrated that neural stem and progenitor cells lead to the most clinically promising results. Endogenous activation of neural precursors has also been explored based on the fact that resident precursor cells have the inherent capacity to proliferate, migrate and differentiate into mature neurons in the uninjured adult brain. Studies have revealed that these neural precursor cell behaviours can be activated following stroke, whereby neural precursors will expand in number, migrate to the infarct site and differentiate into neurons. However, this innate response is insufficient to lead to functional recovery, making it necessary to enhance the activation of endogenous precursors to promote tissue repair and functional recovery. Herein we will discuss the current state of the stem cell-based approaches with a focus on endogenous repair to treat the stroke injured brain.

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“…Similar results were seen following intravenous injection of human MSCs overexpressing placental growth factor (PIGF) [69]. Studies involving stereotactic transplants of cells modified to overexpress BDNF [90], GDNF [91], HIF-1α [92], NT-3 [93], NGF [94], and Noggin [94] have also positively impacted lesion size, functional recovery, and angiogenesis.…”

Section: Altering Cell Secretory Profilementioning

confidence: 71%

Intravascular Stem Cell Transplantation for Stroke

Auriat

Rosenblum

Smith

et al. 2011

Transl. Stroke Res.

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Stroke is the third leading cause of death and the leading cause of adult disability in North America. Emphasis has been placed on developing treatments that reduce the devastating long-term impacts of this disease, and preclinical research on stem cell therapy has demonstrated promising results. However, questions about the optimal cell delivery method and timing of cell transplantation are not fully answered. Recent findings suggest that intravascular stem cell delivery is a safe and efficacious alternative to stereotactic cell injections. It also offers advantages should repeat treatments prove beneficial. Recent reports further suggest that intra-arterial injection results in a wider distribution of cells throughout the stroked hemisphere with a significantly greater cell engraftment compared to intravenous injection. In this review, we describe the benefits and potential risks associated with intravascular stem cell delivery and compare intra-arterial to intravenous cell transplantation methods. We discuss the importance of cell biodistribution and timing of transplantation in driving cell survival. We examine current proposed mechanisms involved in cell migration and functional recovery and discuss future directions for intravascular stem cell therapy research.

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Transplantation of neural stem cells expressing hypoxia-inducible factor-1α (HIF-1α) improves behavioral recovery in a rat stroke model

Cited by 56 publications

References 30 publications

Neural Stem Cell Protects Aged Rat Brain from Ischemia–Reperfusion Injury through Neurogenesis and Angiogenesis

Neural Stem Cell Protects Aged Rat Brain from Ischemia–Reperfusion Injury through Neurogenesis and Angiogenesis

Role of neural precursor cells in promoting repair following stroke

Intravascular Stem Cell Transplantation for Stroke

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