Human umbilical cord-derived endothelial progenitor cells promote growth cytokines-mediated neorevascularization in rat myocardial infarction

作     者：HU Cheng-heng LI Zhi-ming DU Zhi-min ZHANG Ai-xia YANG Da-ya WU Gui-fu 

作者机构：Division of Cardiology First Affiliated Hospital and Key Laboratory on Assisted Circulation Ministry of Health of China Sun Yat-sen University Guangzhou Guangdong 510080 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2009年第122卷第5期

页      面：548-555页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：The study was supported by grants from the Research Grant of the Department of Guangdong Science and Technology (No. 2003C30603)  Natural Science Foundation of Guangdong Province (No. 5001680) and National Natural Science Foundation of China (No. 30770896).Acknowledgement: The authors would like to thank Mr. DAI Gang and Dr. CHEN Long for their technical assistance in cell isolation  animal model and confocal microscopy 

主　　题：human umbilical cord blood endothelial progenitor cells acute myocardial infarction neovascularization 

摘      要：Background Cell-based vascular therapies of endothelial progenitor cells （EPCs） mediated neovascularization is still a novel but promising approach for the treatment of ischemic disease. The present study was designed to investigate the therapeutic potentials of human umbilical cord blood-derived EPCs （hUCB-EPCs） in rat with acute myocardial infarction. Methods Human umbilical cord blood （hUCB） mononuclear cells were isolated using density gradient centrifugation from the fresh human umbilical cord in healthy delivery woman, and cultured in M199 medium for 7 days. The EPCs were identified by double-positive staining with 1,1＇-dioctadecyl-3,3,3＇,3＇-tetramethylindocarbocyanine percholorate-labeled acetylated low-density lipoprotein （DiI-Ac-LDL） and fluorescein isothiocyanate-conjugated Ulex europaeus lectin （FITC-UEA-I）. The rat acute myocardial infarction model was established by the ligation of the left anterior descending artery. The hUCB-EPCs were intramyocardially injected into the peri-infarct area. Four weeks later, left ventricular function was assessed by a pressure-volume catheter. The average capillary density （CAD） was evaluated by anti-VIII immunohistochemistry staining to reflect the development of neovascularization at the peri-infarct area. The graft cells were identified by double immunofluorescence staining with human nuclear antigen （HNA） and CD31 antibody, representing human origin of EPCs and vascular endothelium, respectively. Expressions of cytokines, proliferating cell nuclear angigen （PCNA）, platelet endothelial cell adhesion molecule （PECAM） and vascular endothelial growth factor （VEGF） were detected to investigate the underlying mechanisms of cell differentiation and revascularization. Results The donor EPCs were detectable and integrated into the host myocardium as confirmed by double-positive immunofluorescence staining with HNA and CD31. And the anti-VIII staining demonstrated a higher degree of microvessel formation in EPCs transplanted