Neurogenic effect of vascular endothelial growth factor during germ layer formation of human embryonic stem cells

Kim, Byung Kak; Kim, Sung Eun; Shim, Ji Sung; Woo, Dong Hun; Gil, Jung Eun; Kim, Suel Kee; Kim, Jong Hoon

doi:10.1016/j.febslet.2006.09.053

Cited by 28 publications

(27 citation statements)

References 36 publications

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“…These revealed that in the differentiation of hESCs, VEGF could promote neural stem cell proliferation. The study from Kim [20] reported that VEGF could up-regulate the expression of neuroectodermal Sox1 and Nestin gene, which were consistent with the findings in this study. Our study further confirmed that VEGF inhibited neural stem cells differentiated into glial cells, and illustrated indirectly those neural stem cells treated with VEGF had greater potential to differentiate into neurons (the data that VEGF directly promotes neuron proliferation were not shown).…”

Section: Discussionsupporting

confidence: 94%

Effect of VEGF on neural differentiation of human embryonic stem cells in vitro

Jiao

et al. 2009

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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The effects of vascular endothelial growth factor (VEGF) on neural differentiation of human embryonic stem cells (hESCs) in vitro and the possible mechanism were observed. The hESCs lines, TJMU1 and TJMU2, were established and stored by our laboratory. hESCs differentiated into neuronal cells through embryonic body formation. In this induction process, hESCs were divided into three groups: group A, routine induction; group B, routine induction+10 ng/mL VEGF; group C, routine induction+10 ng/mL VEGF+10 ng/mL VEGFR2/Fc. OCT4, Nestin and GFAP in each group were detected by RT-PCR, and the cells expressing Nestin and GFAP were counted by immunofluorescence. The percentage of Nestin positive cells in group B was significantly higher than in groups A and C, while the percentage of GFAP positive cells in group B was significantly lower than in groups A and C (P<0.01). There was no significant difference between groups A and C (P>0.05). It was concluded that VEGF, via VEGFR2, stimulated the neural differentiation of hESCs in vitro.

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Section: Discussionsupporting

confidence: 94%

Effect of VEGF on neural differentiation of human embryonic stem cells in vitro

Jiao

et al. 2009

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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“…Neurotrophins such as brain-derived neurotrophic factor and growth factors such as vascular endothelial growth factor and fibroblast growth factor 2 are released from endothelial cells [31,32] and influence neuronal survival, proliferation and differentiation [33]. Thus, an increased release of these growth factors, due to an increase in angiogenesis, may contribute to the foetal neurogenic niche and mediate the proliferative effect; this warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Intrauterine Growth Restriction: Effects on Neural Precursor Cell Proliferation and Angiogenesis in the Foetal Subventricular Zone

et al. 2015

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Exposure to adverse prenatal factors can result in abnormal brain development, contributing to the aetiology of several neurological disorders. Intrauterine insults could occur during neurogenesis and gliogenesis, disrupting these events. Here we investigate the effects of chronic placental insufficiency (CPI) on cell proliferation and the microenvironment in the subventricular zone (SVZ). At 30 days of gestation (DG; term ∼67 DG), CPI was induced in pregnant guinea pigs via unilateral uterine artery ligation to produce growth-restricted (GR) foetuses (n = 7); controls (n = 6) were from the unoperated horn. At 60 DG, foetal brains were stained immunohistochemically to identify proliferating cells (Ki67), immature neurons (polysialylated neuronal cell adhesion molecule), astrocytes (glial fibrillary acidic protein), microglia (ionised calcium-binding adaptor molecule-1, Iba-1) and the microvasculature (von Willebrand factor) in the SVZ. There was no overall difference (p > 0.05) in the total number of Ki67-immunoreactive (IR) cells, the percentage of SVZ occupied by blood vessels or the density of Iba-1-IR microglia in control versus GR foetuses. However, regression analysis across both groups revealed that both the number of Ki67-IR cells and the percentage of SVZ occupied by blood vessels in the ventral SVZ were negatively correlated (p < 0.05) with brain weight. Furthermore, in the SVZ (dorsal and ventral) the density of blood vessels positively correlated (p < 0.05) with the number of Ki67-IR cells. Double-labelling immunofluorescence suggested that the majority of proliferating cells were likely to be neural precursor cells. Thus, we have demonstrated an association between angiogenesis and neurogenesis in the foetal neurogenic niche and have identified a window of opportunity for the administration of trophic support to enhance a neuroregenerative response.

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“…VEGF-A stimulates dopaminergic neuron development in vitro in prenatal rat mesencephalic explants (Silverman et al, 1999). VEGF-A application during the formation of embryoid bodies from human embryonic stem cells promotes the generation of neuroectodermal cells, which are differentiating mainly into neurons retaining a dopaminergic phenotype (Kim et al, 2006). Mice lacking hypoxia-inducible factor-1, which have lower VEGF-A levels in the brain, develop fewer dopaminergic neurons (Milosevic et al, 2007).…”

Section: Flt-1tkmentioning

confidence: 99%

VEGFR-1 Regulates Adult Olfactory Bulb Neurogenesis and Migration of Neural Progenitors in the Rostral Migratory Stream In Vivo

Wittko¹,

Schänzer²,

Kuzmichev³

et al. 2009

Journal of Neuroscience

103

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The generation of new neurons in the olfactory bulb (OB) persists into adulthood and is a multistep process that includes proliferation, fate choice, migration, survival, and differentiation. Neural precursor cells destined to form olfactory interneurons arise in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) to the OB. Recently, some factors classically known from their effects on the vascular system have been found to influence different steps of adult neurogenesis. In the present study, we report a modulatory function for the vascular endothelial growth factor receptor-1 (VEGFR-1) in adult olfactory neurogenesis. We identified expression of VEGFR-1 in GFAP-positive cells within regions involved in neurogenesis of the adult mouse brain. To determine functions for VEGFR-1 in adult neurogenesis, we compared neural progenitor cell proliferation, migration, and differentiation from wild-type and VEGFR-1 signaling-deficient mice (Flt-1TK Ϫ/Ϫ mice). Our data show that VEGFR-1 signaling is involved in the regulation of proliferation of neuronal progenitor cells within the SVZ, migration along the RMS, and in neuronal differentiation and anatomical composition of interneuron subtypes within the OB. RMS migration in Flt-1TK Ϫ/Ϫ mice was altered mainly as a result of increased levels of its ligand VEGF-A, which results in an increased phosphorylation of VEGFR-2 in neuronal progenitor cells within the SVZ and the RMS. This study reveals that proper RMS migration is dependent on endogenous VEGF-A protein.

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Neurogenic effect of vascular endothelial growth factor during germ layer formation of human embryonic stem cells

Cited by 28 publications

References 36 publications

Effect of VEGF on neural differentiation of human embryonic stem cells in vitro

Effect of VEGF on neural differentiation of human embryonic stem cells in vitro

Intrauterine Growth Restriction: Effects on Neural Precursor Cell Proliferation and Angiogenesis in the Foetal Subventricular Zone

VEGFR-1 Regulates Adult Olfactory Bulb Neurogenesis and Migration of Neural Progenitors in the Rostral Migratory Stream In Vivo

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