There is a pressing need for new approaches to prevent stroke. Endothelial progenitor cells (EPCs) promote vascular repair and revascularization in the ischemic brain. The present study sought to evaluate whether preventive delivery of EPCs could prevent or protect against stroke. Stroke-prone spontaneously hypertensive rats (SHR-SP) received a single injection of EPCs, and their survival time was monitored. In addition, at 28 and/or 42 days after a single injection of EPCs, SHR-SP and mice were subjected to cerebral ischemia, and cerebral ischemic injury, local angiogenesis and in vivo EPC integration were determined. Other experiments examined the effects of EPC conditioned medium, and the distribution of donor EPCs taken from GFP transgenic mice. It was found that EPC-pretreated SHR-SP showed longer lifespans than untreated controls. A single preventive injection of EPCs could produce persistent protective effects against cerebral ischemic injury (lasting at least 42 days), and promote local angiogenesis in the ischemic brain, in two types of animals (SHR-SP and normotensive mice). EPCs of donor origin could be detected in the recipient peripheral blood, and integrated into the recipient ischemic brains. Furthermore, it was suggested that mouse EPCs might exert paracrine effects on cerebral ischemic injury in addition to their direct angiogenic effects. In conclusion, a single preventive injection of EPCs prolonged the lifespan of SHR-SP, and protected against cerebral ischemic injury for at least 7 weeks. It is implied that EPC injection might be a promising candidate for a preventive role in patients at high risk for stroke.
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August 2018
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Research Article|
August 30 2018
A preventive injection of endothelial progenitor cells prolongs lifespan in stroke-prone spontaneously hypertensive rats
Cheng Peng;
Cheng Peng
*
1School of Public Health and Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Xiao-Hui Dong;
Xiao-Hui Dong
*
2Department of Pharmacy, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
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Jia-Lin Liu;
Jia-Lin Liu
*
1School of Public Health and Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Yu-Long Tao;
Yu-Long Tao
5Department of Pharmacy, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai 200120, China
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Chun-Fang Xu;
Chun-Fang Xu
3Department of Identification of Traditional Chinese Medicine and Department of Pharmacology, The Second Military Medical University, Shanghai 200433, China
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Li-Ping Wang;
Li-Ping Wang
1School of Public Health and Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Chun-Long Liu;
Chun-Long Liu
1School of Public Health and Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Ding-Feng Su;
Ding-Feng Su
3Department of Identification of Traditional Chinese Medicine and Department of Pharmacology, The Second Military Medical University, Shanghai 200433, China
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Xia Tao;
Xia Tao
5Department of Pharmacy, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai 200120, China
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Chuan Zhang;
Chuan Zhang
3Department of Identification of Traditional Chinese Medicine and Department of Pharmacology, The Second Military Medical University, Shanghai 200433, China
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Alex F. Chen;
4Third Xiangya Hospital and the Institute of Vascular Disease and Translational Medicine, Central South University, Changsha, Hunan 410013, China
6Institute of Development and Regenerative Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092
Correspondence: He-Hui Xie (xhhtom@263.net) and Alex F Chen (chena5@upmc.edu)
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He-Hui Xie
1School of Public Health and Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
3Department of Identification of Traditional Chinese Medicine and Department of Pharmacology, The Second Military Medical University, Shanghai 200433, China
4Third Xiangya Hospital and the Institute of Vascular Disease and Translational Medicine, Central South University, Changsha, Hunan 410013, China
Correspondence: He-Hui Xie (xhhtom@263.net) and Alex F Chen (chena5@upmc.edu)
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Publisher: Portland Press Ltd
Received:
May 04 2018
Revision Received:
July 06 2018
Accepted:
July 10 2018
Accepted Manuscript online:
July 13 2018
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (16): 1797–1810.
Article history
Received:
May 04 2018
Revision Received:
July 06 2018
Accepted:
July 10 2018
Accepted Manuscript online:
July 13 2018
Citation
Cheng Peng, Xiao-Hui Dong, Jia-Lin Liu, Yu-Long Tao, Chun-Fang Xu, Li-Ping Wang, Chun-Long Liu, Ding-Feng Su, Xia Tao, Chuan Zhang, Alex F. Chen, He-Hui Xie; A preventive injection of endothelial progenitor cells prolongs lifespan in stroke-prone spontaneously hypertensive rats. Clin Sci (Lond) 31 August 2018; 132 (16): 1797–1810. doi: https://doi.org/10.1042/CS20180360
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