Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (6): 1286-1292.doi: 10.4103/1673-5374.358609

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Overexpression of vascular endothelial growth factor enhances the neuroprotective effects of bone marrow mesenchymal stem cell transplantation in ischemic stroke

Cui Liu1, 2, #, Zhi-Xiang Yang1, #, Si-Qi Zhou1, Ding Ding1, Yu-Ting Hu1, Hong-Ning Yang1, 3, Dong Han1, 3, Shu-Qun Hu1, 3, *, Xue-Mei Zong1, 4, *   

  1. 1Institute of Emergency Rescue Medicine, Emergency Center, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China; 2Emergency Department of Affiliated Lianyungang Hospital of Xuzhou Medical University/The First People’s Hospital of Lianyungang, Lianyungang, Lianyungang, Jiangsu Province, China; 3Laboratory of Emergency Medicine, Second Clinical Medical College of Xuzhou Medical University, Xuzhou Medical University, Xuzhou, Jiangsu Province, China; 4Key Laboratory of Brain Diseases Bioinformation, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
  • Online:2023-06-15 Published:2023-01-05
  • Contact: Xue-Mei Zong, MD, xuemeizong@xzhmu.edu.cn; Shu-Qun Hu, PhD, hushuqun88@xzhmu.edu.cn.
  • Supported by:
    This study was supported by Key Research and Development Plan of Xuzhou Science and Technology Bureau, No. KC21162 (to XMZ), a grant from Jiangsu Key Laboratory of Brain Disease Bioinformationg, No. XZSYSKF2021018 (to XMZ), Natural Science Fund for Colleges and Universities in Jiangsu Province, No. 19KJB320024 (to HNY), the Science and Technology Development Fund from Affiliated Hospital of Xuzhou Medical University, Nos. XYFM2021024 (to XMZ), XYFM2021006 (to DH).

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Abstract: Although bone marrow mesenchymal stem cells (BMSCs) might have therapeutic potency in ischemic stroke, the benefits are limited. The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor (VEGF) on behavioral defects in a rat model of transient cerebral ischemia, which was induced by middle cerebral artery occlusion. VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke. We found that compared with the stroke-only group and the vehicle- and BMSCs-control groups, the VEGF-BMSCs treated animals displayed the largest benefits, as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke. Additionally, VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier, increased the regeneration of blood vessels in the region of ischemic penumbra, and reducedneuronal degeneration surrounding the infarct core. Further mechanistic studies showed that among all transplant groups, VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor. These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available. 

Key words: bone marrow mesenchymal stem cell, brain-derived neurotrophic factor, CD31, microtubule associated protein 2, middle cerebral artery occlusion, stroke, transplantation, vascular endothelial growth factor