Encapsulated vascular endothelial growth factor—secreting cell grafts have neuroprotective and angiogenic effects on focal cerebral ischemia

Yano, Akimasa; Shingo, Tetsuro; Takeuchi, Akihiro; Yasuhara, Takao; Kobayashi, Kazuki; Takahashi, Kazuya; Muraoka, Kenichiro; Matsui, Toshihiro; Miyoshi, Yasuyuki; Hamada, Hirofumi; Date, Isao

doi:10.3171/jns.2005.103.1.0104

Cited by 62 publications

(44 citation statements)

References 42 publications

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“…38 Recently, encapsulated cell grafts overexpressing VEGF were implanted into rat striatum before induction of focal cerebral ischemia resulting in brain edema. 39 more pertinent than corrective measures. In this conservative view, the idea of augmenting existing angiogenesis without 'triggering' an over-robust response may be critical.…”

Section: Vascular Endothelial Growth Factor Therapymentioning

confidence: 99%

Mechanisms and targets for angiogenic therapy after stroke

Navaratna

Guo

Arai

et al. 2009

Cell Adhesion & Migration

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Stroke remains a major health problem worldwide, and is the leading cause of serious long-term disability. Recent findings now suggest that strategies to enhance angiogenesis after focal cerebral ischemia may provide unique opportunities to improve clinical outcomes during stroke recovery. In this mini-review, we survey emerging mechanisms and potential targets for angiogenic therapies in brain after stroke. Multiple elements may be involved, including growth factors, adhesion molecules and progenitor cells. Furthermore, cross talk between angiogenesis and neurogenesis may also provide additional substrates for plasticity and remodeling in the recovering brain. A better understanding of the molecular interplay between all these complex pathways may lead to novel therapeutic avenues for tackling this difficult disease.

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Section: Vascular Endothelial Growth Factor Therapymentioning

confidence: 99%

Mechanisms and targets for angiogenic therapy after stroke

Navaratna

Guo

Arai

et al. 2009

Cell Adhesion & Migration

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“…76 The ability of transplanted cells to increase endogenous levels of angiogenic factors (such as the aforementioned VEGF, fibroblast growth factor, and BDNF) and chemoattractant factors (for example, SDF-1) induces the proliferation of existing vascular endothelial cells (angiogenesis) and mobilization and homing of endogenous endothelial progenitors (vasculogenesis). Yano and associates 92 have demonstrated that encapsulated cells producing VEGF significantly increase endogenous angiogenesis and improve functional outcome after stroke. The direct injection of recombinant SDF-1 into the stroke-affected rat brain resulted in the increased recruitment of BMSCs and increased vascular density in the ischemic brain.…”

Section: Stem Cell-induced Angiogenesismentioning

confidence: 99%

Intravascular cell replacement therapy for stroke

Guzman

Choi²,

Gera³

et al. 2008

FOC

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✓ The use of stem cell transplantation to restore neurological function after stroke is being recognized as a potential novel therapy. Before stem cell transplantation can become widely applicable, however, questions remain about the optimal site of delivery and timing of transplantation. In particular, there seems to be increasing evidence that intravascular cell delivery after stroke is a viable alternative to intracerebral transplantation. In this review, the authors focus on the intravascular delivery of stem cells for stroke treatment with an emphasis on timing, transendothelial migration and possible mechanisms leading to neuroprotection, angiogenesis, immunomodulation, and neural plasticity. They also review current concepts of in vivo imaging and tracking of stem cells after stroke.

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“…phVEGF was injected slowly into the temporal muscle at three sites in a line at 5-mm intervals with a 50-ml microsyringe (Hamilton, Inc., Reno, N.Y., U.S.A.). A total volume of 0.1 ml of 0.9% saline containing phVEGF (25,50,75,100,125,150,175, and 200 mg) was delivered to each of 12 rats. A volume of 0.1 ml of 0.9% saline was administered to 16 control rats.…”

Section: Methodsmentioning

confidence: 99%

“…3,11,12,16,23) Many experimental studies on VEGF administration have shown effectiveness against brain ischemia in various models. 9,10,15,17,19,21,22,[24][25][26] VEGF was administered by various methods, including VEGF protein, 24) plasmid-containing VEGF complementary deoxyribonucleic acid (cDNA), 13) adeno-associated viral vector-mediated VEGF cDNA, 15,21) VEGF gene-transformed bone marrow stromal cells engineered with a herpes simplex virus, 17) encapsulated transformed kidney cellsproducing VEGF, 25) and others. We previously reported that administration of plasmid human VEGF (phVEGF) combined with indirect vasoreconstructive surgery significantly increased angiogenesis in the rat ischemia model.…”

Section: Introductionmentioning

confidence: 99%

“…We previously reported that administration of plasmid human VEGF (phVEGF) combined with indirect vasoreconstructive surgery significantly increased angiogenesis in the rat ischemia model. 13) VEGF also increases vascular permeability leading to brain edema, 9,15,20,25,26) so might cause adverse effects including brain edema, resulting in complications related to the clinical use of phVEGF. 15,20,25) Therefore, evaluation of the most effective but safe dose of phVEGF is critical point for clinical application of phVEGF in human patients with brain ischemia.…”

Section: Introductionmentioning

confidence: 99%

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Optimal Dose of Plasmid Vascular Endothelial Growth Factor for Enhancement of Angiogenesis in the Rat Brain Ischemia Model

Katsumata

Sugiu

Tokunaga

et al. 2010

Neurol. Med. Chir.(Tokyo)

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Vascular endothelial growth factor (VEGF) administration has recently been assessed as a therapeutic strategy for ischemic diseases including brain ischemia because of its angiogenic effect. However, VEGF also causes detrimental adverse effects by increasing vascular permeability. This study examined whether plasmid human VEGF (phVEGF) administration induced angiogenic effects in the rat brain ischemia model caused by permanent ligation of both common carotid arteries, and investigated the occurrence of adverse effects. Administration of various doses (0-200 mg) of phVEGF in the temporal muscle was followed by encephalo-myo-synangiosis. Thirty days after treatment, the numbers and areas of capillaries per field in the extracted brains were analyzed with the National Institutes of Health Image software program. The maximal angiogenic effect occurred with a 100 mg dose of phVEGF in the numbers and areas of capillaries in the VEGF-treated brains. Histological examination showed no apparent adverse effects in the brain parenchyma even at the highest administration dose (200 mg) of phVEGF. The maximal angiogenic effect at the optimal dose of phVEGF can be considered under the threshold to cause serious adverse effects in the rat brain.

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Encapsulated vascular endothelial growth factor—secreting cell grafts have neuroprotective and angiogenic effects on focal cerebral ischemia

Abstract: Continuous intracerebral administration of low-dose VEGF165 through encapsulated grafts of VEGF-producing cells produces neuroprotective and angiogenic effects. These effects improve subsequent motor function.

Cited by 62 publications

References 42 publications

Mechanisms and targets for angiogenic therapy after stroke

Mechanisms and targets for angiogenic therapy after stroke

Intravascular cell replacement therapy for stroke

Optimal Dose of Plasmid Vascular Endothelial Growth Factor for Enhancement of Angiogenesis in the Rat Brain Ischemia Model

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