A preventive injection of endothelial progenitor cells prolongs lifespan in stroke-prone spontaneously hypertensive rats

2018 ◽  
Vol 132 (16) ◽  
pp. 1797-1810 ◽  
Author(s):  
Cheng Peng ◽  
Xiao-Hui Dong ◽  
Jia-Lin Liu ◽  
Yu-Long Tao ◽  
Chun-Fang Xu ◽  
...  

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.

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao-Hui Dong ◽  
Cheng Peng ◽  
Yu-Yi Zhang ◽  
Yu Jiang ◽  
Li-Jun Yang ◽  
...  

It is of great clinical significance to develop potential novel strategies to prevent cardio-cerebrovascular complications in patients with hyperlipidemia. Vascular Endothelial integrity and function play a key role in the prevention of cardio-cerebrovascular diseases. Endothelial progenitor cells (EPCs) can home to sites of ischemic injury and promote endothelial regeneration and neovascularization. Hypercholesterolemia impairs the function of EPC. The present study attempted to identify the effect of piperlongumine on EPCs’ angiogenic potential and cerebral ischemic injury in high-fat diet-fed (HFD-fed) mice. Here, we showed that treatment with low-does piperlongumine (0.25 mg/kg/day) for 8 weeks significantly improved EPCs function and reduced the cerebral ischemic injury (both infarct volumes and neurobehavioral outcomes) in HFD-fed mice. In addition, low-dose piperlongumine administration increased intracellular NO level and reduced intracellular O2- level in EPCs of HFD-fed mice. Moreover, incubation with piperlongumine (1.0 μM, 24 h) reduced thrombospondin-1/2 (TSP-1/2, a potent angiogenesis inhibitor) expression levels in EPCs from HFD-fed mice, increased the therapeutic effect of EPC from HFD-fed mice on cerebral ischemic injury reduction and angiogenesis promotion in HFD-fed mice, and the donor derived EPCs homed to the recipient ischemic brain. In conclusion, low-dose piperlongumine can enhance EPCs’ angiogenic potential and protect against cerebral ischemic injury in HFD-fed mice. It is implied that treatment with low-dose piperlongumine might be a potential option to prevent ischemic diseases (including stroke) in patients with hyperlipidemia, and priming with piperlongumine might be a feasible way to improve the efficacy of EPC-based therapy for ischemic diseases.


2018 ◽  
Vol 45 (1) ◽  
pp. 175-191 ◽  
Author(s):  
Cheng Peng ◽  
Li-Ping Wang ◽  
Xia Tao ◽  
Xiao-Hui Dong ◽  
Chun-Fang Xu ◽  
...  

Background/Aims: Chronic cold exposure may increase energy expenditure and contribute to counteracting obesity, an important risk factor for cerebrocardiovascular diseases. This study sought to evaluate whether preventive cold acclimation before ischemia onset might be a promising option for preventing cerebral ischemic injury. Methods: After a 14-day cold acclimation period, young and aged mice were subjected to permanent cerebral ischemia, and histological analyses and behavioral tests were performed. Mouse endothelial progenitor cells (EPCs) were isolated, their function and number were determined, and the effects of EPC transplantation on cerebral ischemic injury were investigated. Results: Preventive cold acclimation before ischemia onset increased EPC function, promoted ischemic brain angiogenesis, protected against cerebral ischemic injury, and improved long-term stroke outcomes in young mice. In addition, transplanted EPCs from cold-exposed mice had a greater ability to reduce cerebral ischemic injury and promote local angiogenesis compared to those from control mice, and EPCs from donor animals could integrate into the recipient ischemic murine brain. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury, which could be improved by preventive cold acclimation. Moreover, preventive cold acclimation could also enhance EPC function, promote local angiogenesis, and protect against cerebral ischemic injury in aged mice. Conclusions: Preventive cold acclimation before ischemia onset improved long-term stroke outcomes in mice at least in part via promoting the reparative function of EPC. Our findings imply that a variable indoor environment with frequent cold exposure might benefit individuals at high risk for stroke.


Stroke ◽  
2011 ◽  
Vol 42 (9) ◽  
pp. 2571-2577 ◽  
Author(s):  
Naoki Oyama ◽  
Yoshiki Yagita ◽  
Miki Kawamura ◽  
Yukio Sugiyama ◽  
Yasukazu Terasaki ◽  
...  

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