Functional Recovery of Stroke Rats Induced by Granulocyte Colony-Stimulating Factor–Stimulated Stem Cells

Shyu, Woei Cherng; Lin, Shinn Zong; Yang, Hui; Tzeng, Yi Shiuan; Pang, Cheng‐Yoong; Yen, Pao-Sheng; Li, Hung

doi:10.1161/01.cir.0000142616.07367.66

Cited by 325 publications

(294 citation statements)

References 31 publications

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“…To further investigate the effect of G-CSF deficiency on long-term proliferation and to determine the phenotype of the newborn hippocampal cells a BrdU/NeuN imunohistochemistry was performed 6 d after the last BrdU injection. The findings of the current study confirm and exceed the results of an earlier study showing increased neurogenesis in the dentate gyrus of rats treated with G-CSF (Shyu et al, 2004;Schneider et al, 2005;Kawada et al, 2006). Early in vitro studies have already shown that G-CSF has the ability to induce neuronal differentiation phenotypes in adult stem cells, an effect that correlates to in vivo induction of neurogenesis.…”

Section: Discussionsupporting

confidence: 89%

The Role of Granulocyte-Colony Stimulating Factor (G-CSF) in the Healthy Brain: A Characterization of G-CSF-Deficient Mice

Diederich¹,

Sevimli²,

Dörr³

et al. 2009

J. Neurosci.

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Granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor that controls proliferation and differentiation of neural stem cells. Although recent studies have begun to explore G-CSF-related mechanisms of action in various disease models, little is known about its function in the healthy brain. In the present study, the effect of G-CSF deficiency on memory formation and motor skills was investigated. The impact of G-CSF deficiency on the structural integrity of the hippocampus was evaluated by analyzing the generation of doublecortin-expressing cells, the amount of bromodeoxyurine-labeled cells, the dendritic complexity in hippocampal neurons, the binding densities of NMDA and GABA A receptors and the induction of long-term potentiation (LTP). G-CSF deficiency caused a disruption in memory formation and in the development of motor skills. These impairments were associated with reduced ligand binding densities of NMDA receptors in hippocampal subfields CA3 and the dentate gyrus. The reduced excitation was potentiated by increased ligand binding densities of GABA A receptors resulting in a relative shift in favor of inhibition and impaired behavioral performance. These alterations were accompanied by impaired induction of LTP in the CA1 region. Moreover, G-CSF deficiency led to decreased dendritic complexity in hippocampal neurons in the dentate gyrus and the CA1 region. G-CSF deficiency also caused a reduction of neuronal precursor cells in the dentate gyrus. These findings confirm G-CSF as an essential neurotrophic factor, and point to a role in the proliferation, differentiation and functional integration of neural cells necessary for the structural and functional integrity of the hippocampal formation.

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Section: Discussionsupporting

confidence: 89%

The Role of Granulocyte-Colony Stimulating Factor (G-CSF) in the Healthy Brain: A Characterization of G-CSF-Deficient Mice

Diederich¹,

Sevimli²,

Dörr³

et al. 2009

J. Neurosci.

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“…For example, CSF3, NGF, and NT-3 expression was upregulated. Administration of these factors induces neurogenesis and promotes functional recovery after stroke (Shyu et al, 2004;Schneider et al, 2005;Frielingsdorf et al, 2007;Zhang et al, 2008). Expression of TGF␤1 and BMP2 was clearly decreased in MSCs cultured with MSC-treated brain extracts.…”

Section: Discussionmentioning

confidence: 97%

Repeated Mesenchymal Stem Cell Treatment after Neonatal Hypoxia-Ischemia Has Distinct Effects on Formation and Maturation of New Neurons and Oligodendrocytes Leading to Restoration of Damage, Corticospinal Motor Tract Activity, and Sensorimotor Function

Velthoven¹,

Kavelaars²,

Bel³

et al. 2010

Journal of Neuroscience

173

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“…In this regard, exogenous cytokine-induced mobilization of BMCs has been shown to be beneficial after stroke as well as MI [6,28]. Moreover, the identification of BMC-derived cells in various injured tissues, including brain, liver, kidney, lung, and heart, indicates that tissue injury can induce mobilization of BMCs from the marrow into the PB [1][2][3][4][5]7,8].…”

Section: Discussionmentioning

confidence: 99%

Bone marrow-derived pluripotent very small embryonic-like stem cells (VSELs) are mobilized after acute myocardial infarction

Zuba‐Surma

Kucia

Dawn

et al. 2008

Journal of Molecular and Cellular Cardiology

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The adult bone marrow (BM) harbors Sca-1+/Lin−/CD45− pluripotent very small embryonic-like stem cells (VSELs), which can differentiate in vitro into several lineages, including cardiac and vascular lineages. Since mobilization of stem/progenitors from the BM is a prerequisite for their participation in organ repair, we investigated whether VSELs are mobilized into the peripheral blood (PB) after acute myocardial infarction (MI). Wild-type mice (C57/BL6 strain, 6-or 15-wk-old) underwent a 30-min coronary occlusion followed by reperfusion (groups III-V, VIII-X, n=6-12/ group) or a 1-h open-chest state (sham controls, groups II and VII, n=8-12/group); mice were sacrificed 24 h, 48 h, or 7 days later and PB samples were harvested. Controls (groups I and VI, n=6/ group) were sacrificed without any intervention. By flow cytometry, VSELs were barely detectable in PB under baseline conditions but their levels increased significantly at 48 h after MI, both in younger (6-wk-old) and older (15-wk-old) mice (3.33±0.37 and 7.10±0.89 cells/μl of blood, respectively). At 48 h after MI, qRT-PCR analysis revealed significantly increased levels of mRNA of markers of pluripotency (Oct-4, Nanog, Rex-1, Rif1, and Dppa1) in PB cells of 6-wk-old (but not 15-wk-old) infarcted mice compared with either controls or sham controls. Confocal microscopy and ImageStream analysis confirmed that mobilized VSELs expressed Oct-4 protein, while Sca-1+/Lin −/CD45+ hematopoietic stem cells did not. This is the first demonstration that Oct-4+ pluripotent stem cells (VSELs) are mobilized from the BM into the PB after acute MI. This phenomenon may have pathophysiological and therapeutic implications for repair of infarcted myocardium.

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Functional Recovery of Stroke Rats Induced by Granulocyte Colony-Stimulating Factor–Stimulated Stem Cells

Cited by 325 publications

References 31 publications

The Role of Granulocyte-Colony Stimulating Factor (G-CSF) in the Healthy Brain: A Characterization of G-CSF-Deficient Mice

The Role of Granulocyte-Colony Stimulating Factor (G-CSF) in the Healthy Brain: A Characterization of G-CSF-Deficient Mice

Repeated Mesenchymal Stem Cell Treatment after Neonatal Hypoxia-Ischemia Has Distinct Effects on Formation and Maturation of New Neurons and Oligodendrocytes Leading to Restoration of Damage, Corticospinal Motor Tract Activity, and Sensorimotor Function

Bone marrow-derived pluripotent very small embryonic-like stem cells (VSELs) are mobilized after acute myocardial infarction

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