Bone marrow stromal cell transplantation through tail vein injection promotes angiogenesis and vascular endothelial growth factor expression in cerebral infarct area in rats.
OBJECTIVE
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.
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.
Zhihua
Z
Yang
Department of Neurology, the Fifth Affiliated Hospital of Wenzhou Medical college, Zhejiang, China.
Xueli
X
Cai
Department of Neurology, the First Affiliated Hospital of Jinan University, Guangzhou, China. Electronic address: andingxu@gmail.com.
Anding
A
Xu
Department of Neurology, the First Affiliated Hospital of Jinan University, Guangzhou, China.
Fengxia
F
Xu
Department of Neurology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Qin
Q
Liang
D000818:Animals; D001921:Brain / Q000098:blood supply; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002544:Cerebral Infarction / Q000473:pathology / Q000628:therapy*; D005260:Female; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009454:Neurofibrils / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013623:Tail; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat
Ki-67; VEGF; cerebral infarction; mesenchymal stromal cells