Transplantation of VEGF-mediated bone marrow mesenchymal stem cells promotes functional improvement in a rat acute cerebral infarction model.

Abstract

Vascular endothelial growth factor (VEGF) stimulation and bone marrow mesenchymal stem cell (BMSC) transplantation have been implicated in the treatment of acute cerebral infarction for their pivotal roles in behavioral recovery, neuroprotection, neurogenesis, and angiogenesis. However, the effects of BMSC transplants are likely limited because of low transplant survival after acute cerebral infarction, and delivery of VEGF alone also has limited effects on recovery because the protein is cleared quickly. This study attempted to explore whether VEGF could be transferred into BMSC via an adenovirus and whether transplanting VEGF-transfected BMSC into the rat brain provides sufficient neuroprotection after transient middle cerebral artery occlusion. The adenovirus carried VEGF into BMSC (Ad-VEGF-BMSC), and purified adenovirus was transferred into BMSC (Ad-BMSC). Western blots were used to detect the expression of VEGF protein after transfection. Rats exposed to 90-min middle cerebral artery occlusion (MCAO) were treated with Ad-VEGF-BMSC, Ad-BMSC, BMSC and Dulbecco's Modified Eagle's Medium (DMEM) after ischemia reperfusion for 24h. The Sham group only received surgery. After transplantation of Ad-VEGF-BMSC into the perifocal area of the ischemic rat brain, we found increased expression and secretion of VEGF and BDNF as well as a higher level of MAP2, increased microvascular density, improved behavioral function and enhanced BMSC survival. Our results indicated that transplantation of Ad-VEGF-BMSC improved ischemic neurological deficiency after MCAO in rats. This finding provides a potential valuable therapeutic intervention for cerebral ischemic diseases.

• Authors: Xuemei Zong, Shuguang Wu, Fujun Li, Lanxin Lv, Dong Han, Ningjun Zhao, Xianliang Yan, Shuqun Hu, Tie Xu
• Journal: Brain research (Brain Res) Vol. 1676 Pg. 9-18 (Dec 01 2017) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 28823954 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier B.V.

Chemical References

• Brain-Derived Neurotrophic Factor
• MAP2 protein, rat
• Microtubule-Associated Proteins
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, rat
• Green Fluorescent Proteins

Topics

• Adenoviridae (genetics)
• Animals
• Brain-Derived Neurotrophic Factor (metabolism)
• Cell Survival
• Cerebral Infarction (metabolism, pathology, therapy)
• Disease Models, Animal
• Genetic Vectors
• Green Fluorescent Proteins (genetics, metabolism)
• HEK293 Cells
• Humans
• Male
• Mesenchymal Stem Cell Transplantation (methods)
• Mesenchymal Stem Cells (metabolism)
• Microtubule-Associated Proteins (metabolism)
• Microvessels (metabolism, pathology)
• Neuroprotection
• Random Allocation
• Rats, Sprague-Dawley
• Vascular Endothelial Growth Factor A (administration & dosage, genetics, metabolism)