中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (6): 1286-1292.doi: 10.4103/1673-5374.358609

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

过表达血管内皮生长因子的骨髓间充质干细胞移植对缺血性脑卒中的神经保护

  

  • 出版日期:2023-06-15 发布日期:2023-01-05
  • 基金资助:
    徐州市科技局重点研发计划（KC21162），江苏脑疾病生物信息重点实验室资助项目（XZSYSKF2021018 ），徐州市医科大学附属医院资助项目（XYFM2021024）， 江苏省高等院校自然科学基金（19KJB320024），徐州医学院附属医院科技发展基金 （XYFM2021006）

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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摘要：

骨髓间充质干细胞移植对缺血性脑卒中有治疗作用；然而，其治疗效果仍不十分令人满意。为了解过表达血管内皮生长因子的骨髓间充质干细胞移植对短暂性脑缺血大鼠模型行为障碍的影响，实验在建立大脑中动脉阻塞诱发的短暂性脑缺血大鼠模型后24h，将过表达/未过表达血管内皮生长因子的骨髓间充质干细胞注射到梗死侧纹状体。结果发现，与移植未过表达血管内皮生长因子的骨髓间充质干细胞的大鼠相比，过表达血管内皮生长因子的骨髓间充质干细胞移植在改善脑缺血模型大鼠行为表现和缩小梗死体积方面均显示出最好的效果。同时过表达血管内皮生长因子的骨髓间充质干细胞移植还可以更明显减轻血脑屏障的破坏，促进缺血半影区域的血管再生，并减少梗死核心周围的突触损失和神经元退化。进一步的机制研究表明，过表达血管内皮生长因子的骨髓间充质干细胞移植诱导的脑源性神经营养因子水平也更高。这些上述结果提示，骨髓间充质干细胞过表达血管内皮生长因子后进行移植增强了缺血性脑卒中的治疗效果，在临床应用方面较单独骨髓间充质干细胞移植显示出更大的前景。

https://orcid.org/0000-0003-0010-1664 (Xue-Mei Zong); https://orcid.org/0000-0001-8991-0569 (Shu-Qun Hu)

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