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. 2016 Sep;11(9):1456-1463.
doi: 10.4103/1673-5374.191220.

Transplantation of Vascular Endothelial Growth Factor-Modified Neural Stem/Progenitor Cells Promotes the Recovery of Neurological Function Following Hypoxic-Ischemic Brain Damage

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Free PMC article

Transplantation of Vascular Endothelial Growth Factor-Modified Neural Stem/Progenitor Cells Promotes the Recovery of Neurological Function Following Hypoxic-Ischemic Brain Damage

Yue Yao et al. Neural Regen Res. .
Free PMC article

Abstract

Neural stem/progenitor cell (NSC) transplantation has been shown to effectively improve neurological function in rats with hypoxic-ischemic brain damage. Vascular endothelial growth factor (VEGF) is a signaling protein that stimulates angiogenesis and improves neural regeneration. We hypothesized that transplantation of VEGF-transfected NSCs would alleviate hypoxic-ischemic brain damage in neonatal rats. We produced and transfected a recombinant lentiviral vector containing the VEGF165 gene into cultured NSCs. The transfected NSCs were transplanted into the left sensorimotor cortex of rats 3 days after hypoxic-ischemic brain damage. Compared with the NSCs group, VEGF mRNA and protein expression levels were increased in the transgene NSCs group, and learning and memory abilities were significantly improved at 30 days. Furthermore, histopathological changes were alleviated in these animals. Our findings indicate that transplantation of VEGF-transfected NSCs may facilitate the recovery of neurological function, and that its therapeutic effectiveness is better than that of unmodified NSCs.

Keywords: animal model; cerebral cortex; hypoxic-ischemic brain damage; nerve regeneration; neural regeneration; neural stem/progenitor cells; neuroprotection; transfection; transplantation; vascular endothelial growth factor.

Conflict of interest statement

Conflicts of Interest: None declared.

Figures

Figure 1
Figure 1
Neural stem/progenitor cells identified by immunofluorescence using the marker nestin (red fluorescence). Scale bar: 20 µm.
Figure 2
Figure 2
VEGF gene expression assessed by RT-PCR in the affected brain region post HIBD in the different groups. VEGF mRNA expression levels were quantified by scanning the optical density of the bands and normalizing against GAPDH. Data are expressed as the mean ± SD (5 rats per group). The data for the different groups were compared using one-way analysis of variance followed by Tukey's honestly significant difference test when an overall significance was detected. *P < 0.05, vs. CON group; #P < 0.05, vs. NSCs group or PBS group; †P < 0.05, vs. PBS group. NSCs: Neural stem/progenitor cells; CON: sham-operated control; PBS: phosphate-buffered saline; HIBD: hypoxic-ischemic brain damage; VEGF: vascular endothelial growth factor; M: marker; RT-PCR: reverse transcription-polymerase chain reaction; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase.
Figure 3
Figure 3
VEGF immunoreactivity in the affected brain region post HIBD in the different groups. (A–D) VEGF immunoreactivity in CON, PBS, transgene NSCs and NSCs groups. Scale bars: 20 µm. (E) The quantification of VEGF-immunoreactive cells was performed by immunohistochemical staining of the hippocampal region in hypoxic-ischemic ipsilateral hemispheres. Data are expressed as the mean ± SD (12 rats in each group). The data for the different groups were compared using one-way analysis of variance followed by Tukey's honestly significant difference test when an overall significance was detected. *P < 0.05, vs. CON group; #P < 0.05, vs. NSCs group or PBS group; †P < 0.05, vs. PBS group. NSCs: Neural stem/progenitor cells; CON: sham-operated control; PBS: phosphate-buffered saline; HIBD: hypoxic-ischemic brain damage; VEGF: vascular endothelial growth factor.
Figure 4
Figure 4
Number of neurons in the affected cortex post HIBD in the different groups. (A–D) Changes in the cortex of rats in the CON, PBS, transgene NSCs and NSCs groups (scale bar: 20 µm). (E) Neuron densities were quantified by counting Nisslstained cells. Data are expressed as the mean ± SD (12 rats in each group). The data for the different groups were compared using one-way analysis of variance followed by Tukey's honestly significant difference test when an overall significance was detected. *P < 0.05, vs. CON group; #P < 0.05, vs. NSCs group or PBS group; †P < 0.05, vs. PBS group. NSCs: Neural stem/progenitor cells; CON: sham-operated control; PBS: phosphate-buffered saline; HIBD: hypoxic-ischemic brain damage.

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