Abstract
Endothelial progenitor cells (EPCs), as precursors to endothelial cells, play a significant part in the process of endogenous blood vessel repair and maintenance of endothelial integrity. Adiponectin (APN) is an adipocyte-specific adipocytokine. In this study, we aim to test whether we transplant a combined graft of EPCs transfected with the adiponectin gene into a rat model of cerebral ischemia could improve functional recovery after middle cerebral artery occlusion (MCAO). Sprague-Dawley (SD) rats were randomly divided into a MCAO control group, a MCAO EPC treatment group, and a MCAO LV-APN-EPC treatment group. A focal cerebral ischemia and reperfusion model was induced by the intraluminal suture method. After 2 h of reperfusion, EPCs were transplanted by injection through the tail vein. A rotarod test was conducted to assess behavioral function before MCAO and on days 1, 7, and 14 after MCAO. After 14 d, TTC staining, CD31 immunofluorescence, and TUNEL staining were used to evaluate infarct volume, microvessel density, and cell apoptosis. Results revealed that behavioral function, infarct area percentage, microvessel density, and cell apoptosis rates were more favorable in the LV-APN-EPC treatment group than in the EPC treatment group. These data suggested that gene-modified cell therapy may be a useful approach for the treatment of ischemic stroke.
Highlights
Cerebral ischemic stroke has been recognized as a serious neurological disease that is accompanied by high mortality and morbidity worldwide [1]
After 7 days of culture, we observed that the cells were double positive for Dil-acetylated LDL (ac-LDL) uptake and FITC1-Ulex europaeus agglutinin-1 (UEA-1) binding (Figure 2)
After the LV-APN-Endothelial progenitor cells (EPCs) were administered to the rats through the tail vein, we found that behavioral function was improved, infarct volume rates were decreased, ischemic boundary zone (IBZ) microvascular density was increased, and cell apoptosis rates were decreased and were more favorable than the corresponding results from the EPC treatment group
Summary
Cerebral ischemic stroke has been recognized as a serious neurological disease that is accompanied by high mortality and morbidity worldwide [1]. Most of the neuroprotective compounds developed for ischemic damage are clinically ineffective for acute stroke patients [2, 3]. Thrombolytic drugs such as tissue-type plasminogen activator (rt-PA) and endovascular interventional therapy have been proven effective, they are faced with limitations, such as a narrow time window, low dissolution rates, hemorrhage risk, high cost, and other drawbacks. Cells in the core zone show necrosis, while cells in the penumbra zone show apoptosis It is important in the treatment of cerebral ischemia to improve the blood flow in the penumbra zone to save the nerve cells
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