Bone marrow stromal cell transplantation through tail vein injection promotes angiogenesis and vascular endothelial growth factor expression in cerebral infarct area in rats

Zhihua Yang; Xueli Cai; Anding Xu; Fengxia Xu; Qin Liang

doi:10.1016/j.jcyt.2015.06.005

Bone marrow stromal cell transplantation through tail vein injection promotes angiogenesis and vascular endothelial growth factor expression in cerebral infarct area in rats

Cytotherapy. 2015 Sep;17(9):1200-12. doi: 10.1016/j.jcyt.2015.06.005.

Authors

Zhihua Yang¹, Xueli Cai², Anding Xu³, Fengxia Xu⁴, Qin Liang⁵

Affiliations

¹ Department of Neurology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Department of Neurology, the First Affiliated Hospital of Jinan University, Guangzhou, China.
² Department of Neurology, the Fifth Affiliated Hospital of Wenzhou Medical college, Zhejiang, China.
³ Department of Neurology, the First Affiliated Hospital of Jinan University, Guangzhou, China. Electronic address: andingxu@gmail.com.
⁴ Department of Neurology, the First Affiliated Hospital of Jinan University, Guangzhou, China.
⁵ Department of Neurology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

PMID: 26276003
DOI: 10.1016/j.jcyt.2015.06.005

Abstract

Background aims: This study sought to identify correlations between vascular endothelial growth factor (VEGF) expression after tail-vein injection of rat-derived bone marrow stromal cells (BMSCs) and neurogenesis and angiogenesis in cerebral infarct of rats.

Methods: Rats with intraluminal middle cerebral artery occlusion were injected in a tail vein with Hoechst-labeled BMSCs. Functional recovery from cerebral infarction was observed through the use of a locomotion score. The brains of injected rats were sliced, and Hoechst-labeled BMSCs in the infarct and peri-infarct areas and subventricular zone (SVZ) were detected with the use of fluorescence microscopy. Ki-67 (as a cell proliferation marker) and VEGF expression were determined by means of immunohistochemistry. Neurofibril formation and angiogenesis were examined by means of Bielschowsky staining.

Results: Within 1 to 2 weeks after BMSC injection, rats showed significantly improved locomotion scores compared with rats without BMSC injection (P < 0.01). Viable BMSCs were found in the peri-infarct area. The numbers of Ki-67-positive and VEGF-positive cells in the peri-infarct area and SVZ of injected rats were significantly increased compared with the control group (P < 0.01). Numerous new vessels, neurofibrils and anastomosed vasculatures were present in the infarct area. These neurofibrils mainly surrounded the neovasculatures.

Conclusions: These results indicate that BMSC-transplantation in rats through tail vein injection can increase neurogenesis, perhaps as the result of VEGF-mediated and/or Ki-67-mediated angiogenesis.

Keywords: Ki-67; VEGF; cerebral infarction; mesenchymal stromal cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / blood supply
Cell Proliferation
Cell- and Tissue-Based Therapy / methods
Cerebral Infarction / pathology
Cerebral Infarction / therapy*
Female
Male
Mesenchymal Stem Cell Transplantation / methods*
Mesenchymal Stem Cells / metabolism*
Neovascularization, Physiologic / physiology*
Neurofibrils / physiology
Neurogenesis / physiology*
Rats
Rats, Sprague-Dawley
Recovery of Function
Tail
Vascular Endothelial Growth Factor A / metabolism*

Substances

Vascular Endothelial Growth Factor A
vascular endothelial growth factor A, rat