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经18F-氟脱氧葡萄糖标记的自体骨髓单个核细胞冠状动脉内递送:组织分布及对心肌梗死后猪心脏的影响

Intracoronary delivery of autologous bone marrow mononuclear cells radiolabeled by 18F-fluoro-deoxy-glucose: tissue distribution and impact on post-infarct swine hearts.

作者信息

Qian Haiyan, Yang Yuejin, Huang Ji, Gao Runlin, Dou Kefei, Yang Guosheng, Li Jianjun, Shen Rui, He Zuoxiang, Lu Minjie, Zhao Shihua

机构信息

Department of Cardiology, Fuwai Hospital and Cardiovascular Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China.

出版信息

J Cell Biochem. 2007 Sep 1;102(1):64-74. doi: 10.1002/jcb.21277.

Abstract

Intracoronary injection of the bone marrow-derived mononuclear cells (MNCs) is emerging as a potentially novel therapy for ischemic heart failure. This study was aimed at assessing the efficacy of intracoronary MNC delivery in the myocardium. The in vivo distribution and myocardial homing of intracoronarily delivered MNCs in experimental Chinese swine with acute myocardial infarction (AMI) created by occlusion of left anterior descending (LAD) coronary artery for 90 min. MNCs radiolabeled with 18F-fluoro-deoxy-glucose (18F-FDG) were delivered using a coronary catheter into the infarct-related coronary artery 1 week after AMI. Dual-nuclide single photon emission computed tomography (SPECT) revealed that 1 h after cell infusion, 6.8 +/- 1.8% of 18F-FDG-labeled MNCs occurred in the infarcted myocardium with the remaining activity found primarily in the liver and spleen. In the heart, MNCs were detected predominantly in the under-perfused myocardium. The infused cells retained in the hearts at a rate highly correlated with the under-perfused lesional sizes. Pathological examination further demonstrated that 6 weeks after infusion, compared to controls, the hearts receiving MNCs exhibited less fibrosis and inflammatory infiltrate, more viable tissue, and higher vascular density. Cardiac function was significantly improved in the MNC-infused hearts. Thus, 18F-FDG labeling and dual-nuclide SPECT imaging is capable of monitoring in vivo distribution and homing of MNCs after intracoronary infusion. MNC coronary delivery may improve cardiac function and positive ventricular remodeling in the heart with AMI.

摘要

冠状动脉内注射骨髓来源的单核细胞(MNCs)正在成为一种治疗缺血性心力衰竭的潜在新疗法。本研究旨在评估冠状动脉内注射MNCs对心肌的疗效。在通过闭塞左前降支(LAD)冠状动脉90分钟造成急性心肌梗死(AMI)的实验中国小型猪中,研究冠状动脉内递送的MNCs的体内分布和心肌归巢情况。在AMI后1周,使用冠状动脉导管将用18F-氟脱氧葡萄糖(18F-FDG)标记的MNCs递送至梗死相关冠状动脉。双核素单光子发射计算机断层扫描(SPECT)显示,细胞输注后1小时,18F-FDG标记的MNCs中有6.8±1.8%出现在梗死心肌中,其余活性主要在肝脏和脾脏中发现。在心脏中,MNCs主要在灌注不足的心肌中被检测到。输注的细胞在心脏中的保留率与灌注不足的病变大小高度相关。病理检查进一步表明,输注后6周,与对照组相比,接受MNCs的心脏表现出更少的纤维化和炎性浸润、更多的存活组织以及更高的血管密度。输注MNCs的心脏的心脏功能得到显著改善。因此,18F-FDG标记和双核素SPECT成像能够监测冠状动脉内输注后MNCs的体内分布和归巢情况。冠状动脉内递送MNCs可能改善AMI心脏的心脏功能和正向心室重塑。

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