Combined treatment of vascular endothelial growth factor and human neural stem cells in experimental focal cerebral ischemia

Chu, Kon; Park, Kyung‐Il; Lee, Sang Kun; Jung, Keun‐Hwa; Ko, Song-Yi; Kang, Lami; Sinn, Dong-In; Lee, Yong Seok; Kim, Seung Up; Kim, Manho; Roh, Jae-Kyu

doi:10.1016/j.neures.2005.08.010

Cited by 75 publications

(41 citation statements)

References 37 publications

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“…Half the animals in each litter were treated with daily intramuscular injections of rhVEGF165 (20 g/kg), and half were treated with normal saline daily for a total of 13 days from postnatal day 1 through day 14. The doses of rhVEGF165 used in whole animal studies vary widely throughout the literature (3,6,16,38). Daily doses as small as 0.22 g/kg intra-arterially have been used in a rabbit model of limb ischemia (16).…”

Section: Methodsmentioning

confidence: 99%

Recombinant human VEGF treatment transiently increases lung edema but enhances lung structure after neonatal hyperoxia

Kunig¹,

Balasubramaniam²,

Markham³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

103

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human VEGF treatment transiently increases lung edema but enhances lung structure after neonatal hyperoxia. Am J Physiol Lung Cell Mol Physiol 291: L1068 -L1078, 2006. First published July 7, 2006 doi:10.1152/ajplung.00093.2006.-Recent studies suggest that VEGF may worsen pulmonary edema during acute lung injury (ALI), but, paradoxically, impaired VEGF signaling contributes to decreased lung growth during recovery from ALI due to neonatal hyperoxia. To examine the diverse roles of VEGF in the pathogenesis of and recovery from hyperoxia-induced ALI, we hypothesized that exogenous recombinant human VEGF (rhVEGF) treatment during early neonatal hyperoxic lung injury may increase pulmonary edema but would improve late lung structure during recovery. Sprague-Dawley rat pups were placed in a hyperoxia chamber (inspired O2 fraction 0.9) for postnatal days 2-14. Pups were randomized to daily intramuscular injections of rhVEGF165 (20 g/kg) or saline (controls). On postnatal day 14, rats were placed in room air for a 7-day recovery period. At postnatal days 3, 14, and 21, rats were killed for studies, which included body weight and wet-to-dry lung weight ratio, morphometric analysis [including radial alveolar counts (RAC), mean linear intercepts (MLI), and vessel density], and lung endothelial NO synthase (eNOS) protein content by Western blot analysis. Compared with room air controls, hyperoxia increased pulmonary edema by histology and wet-to-dry lung weight ratios at postnatal day 3, which resolved by day 14. Although treatment with rhVEGF did not increase edema in control rats, rhVEGF increased wet-to-dry weight ratios in hyperoxia-exposed rats at postnatal days 3 and 14 (P Ͻ 0.01). Compared with room air controls, hyperoxia decreased RAC and increased MLI at postnatal days 14 and 21. Treatment with VEGF resulted in increased RAC by 181% and decreased MLI by 55% on postnatal day 14 in the hyperoxia group (P Ͻ 0.01). On postnatal day 21, RAC was increased by 176% and MLI was decreased by 58% in the hyperoxia group treated with VEGF. rhVEGF treatment during hyperoxia increased eNOS protein on postnatal day 3 by threefold (P Ͻ 0.05). We conclude that rhVEGF treatment during hyperoxia-induced ALI transiently increases pulmonary edema but improves lung structure during late recovery. We speculate that VEGF has diverse roles in hyperoxiainduced neonatal lung injury, contributing to lung edema during the acute stage of ALI but promoting repair of the lung during recovery. bronchopulmonary dysplasia; lung development; vascular endothelial growth factor; alveolarization; angiogenesis BRONCHOPULMONARY DYSPLASIA (BPD) is the chronic lung disease of infancy that follows ventilator and oxygen therapy for respiratory distress syndrome after premature birth (34). Although the mechanisms underlying BPD are not completely understood, surfactant deficiency, ventilator-induced lung injury, oxygen toxicity, infection, and inflammation are important pathogenic factors (19). Despite improvements in perinatal care over the past decade, the...

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Section: Methodsmentioning

confidence: 99%

Recombinant human VEGF treatment transiently increases lung edema but enhances lung structure after neonatal hyperoxia

Kunig¹,

Balasubramaniam²,

Markham³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

103

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“…The first pass of stem cells injected into the carotid artery would be the brain. Authors of a few studies have explored this route of delivery and have demonstrated functional recovery after stroke 10,17,18 and traumatic brain injury. 11,12 Shen and colleagues 74 injected 2 ϫ 10 6 donor rat BMSCs into the internal carotid artery of rats 24 hours poststroke and successfully induced functional recovery.…”

Section: Route Of Stem Cell Deliverymentioning

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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“…Preclinical data showed that some combined treatments after cerebral ischemia could be an interesting approach and could be more efficient than a cellular or a molecular treatment alone (Chu et al, 2005;Hanabusa et al, 2005;Zhang et al, 2007). We thus hypothesized that EPO administration in combination with MSC may have synergistic effects on neurogenesis and functional recovery after ischemia.…”

Section: Introductionmentioning

confidence: 99%

Combined Therapeutic Strategy Using Erythropoietin and Mesenchymal Stem Cells Potentiates Neurogenesis after Transient Focal Cerebral Ischemia in Rats

Esneault

Pacary

Eddi

et al. 2008

J Cereb Blood Flow Metab

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Many studies showed beneficial effects of either erythropoietin (EPO) or mesenchymal stem cells (MSCs) treatment in cerebral ischemia. In addition to a neuroprotective role, not only EPO but also MSC favors neurogenesis and functional recovery. In an attempt to further improve postischemic tissue repair, we investigated the effect of a systemic administration of MSC, in the presence or not of EPO, on neurogenesis and functional recovery in a transient focal cerebral ischemia model in the adult rat. Twenty-four hours after ischemia, the rats were divided into four groups, namely vehicle, MSC, EPO, and MSC + EPO, and received a single intravenous injection of MSC (2¾10 6 cells) and/or a repeated intraperitoneal administration of EPO (1,000 UI/kg) for 3 days. The lesion volume, the MSC outcome, neurogenesis, and functional recovery were assessed 51 days after ischemia. The results showed that cellular proliferation and neurogenesis were increased along the lateral ventricle wall in the MSC + EPO group, whereas no significant effect was observed in groups receiving MSC or EPO alone. This effect was accompanied by an improvement of mnesic performances. Mesenchymal stem cells expressing neuronal or glial markers were detected in the ischemic hemisphere. These results suggest that EPO could act in a synergistic way with MSC to potentiate the postischemic neurogenesis.

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Combined treatment of vascular endothelial growth factor and human neural stem cells in experimental focal cerebral ischemia

Cited by 75 publications

References 37 publications

Recombinant human VEGF treatment transiently increases lung edema but enhances lung structure after neonatal hyperoxia

Recombinant human VEGF treatment transiently increases lung edema but enhances lung structure after neonatal hyperoxia

Intravascular cell replacement therapy for stroke

Combined Therapeutic Strategy Using Erythropoietin and Mesenchymal Stem Cells Potentiates Neurogenesis after Transient Focal Cerebral Ischemia in Rats

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