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培养于生物降解支架膜内的胚胎干细胞可修复小鼠的梗塞心肌

可庆恩, 杨寅柯, Rana J S, 陈玉, Morgan J P, 萧永福

Beth Israel Deaconess医学中心干细胞研究实验室与Charles A. Dana研究所，Harvard-Thorndike实验室，心血管内科

摘要

作者以往的研究表明，直接在心肌梗塞(myocardial infarction, MI)动物的心脏缺血区注射胚胎干细胞(embryonic stem cells, ESCs)可以提高其心肌功能，干细胞组织工程学可以使组织再生、修复。该研究旨在观察将 ESCs接种到生物降解膜内并移植到梗塞部位的效果。通过结扎小鼠左冠状动脉制作 MI模型，将培养3 d的带有小鼠ESCs的聚羟基乙酸膜(polyglycolic-acid, PGA)移植到心肌缺血及边缘区表面。实验小鼠分成4组：假手术组、 MI组、MI+PGA组、MI+ESC组，移植操作8周后检测血流动力学和心肌功能。 MI组的血压和左心室功能显著降低。与MI组和 MI+PGA组相比， MI+ESC组的血压和心室功能显著改善，存活率也显著增高，在梗塞区检测到 GFP阳性组织，表明ESCs存活，并可能有心肌再生。以上结果表明，移植生物降解膜内的ESCs可修复小鼠梗塞区心肌细胞并提高心脏功能。将 ESCs和生物降解材料联合运用可能为修复受损心脏提供一个新的治疗方法。

关键词： 心肌梗塞; 胚胎干细胞; 支架; 膜; 心肌修复

Embryonic stem cells cultured in biodegradable scaffold repair infarcted myocardium in mice

Ke Qingen, Yang Yinke, Rana J S, Chen Yu, Morgan J P, Xiao Yongfu

The Stem Cells Research Laboratory & The Charles A. Dana Research Institute and Harvard-Thorndike Laboratory, Cardiovascular Division, Beth Israel Deaconess Medical Center

Abstract

Our previous findings demonstrated that directly injecting embryonic stem cells (ESCs) into ischemic region of the heart improved cardiac function in animals with experimental myocardial infarction (MI). Tissue engineering with stem cells may provide tissue creation and repair. This study was designed to investigate the effectiveness of grafting of ESC-seeded biodegradable patch on infarcted heart. MI in mice was induced by ligation of the left coronary artery. Mouse ESCs were seeded on polyglycolic-acid (PGA) material patches. Three days after culture, an ESC-seeded patch was transplanted on the surface of ischemic and peri-ischemic myocardium. Eight weeks after MI operation and patch transplantation, hemodynamics and cardiac function were evaluated in four (sham-operated, MI, MI + cell-free patch, and MI + ESC-patch) groups of mice. The blood pressure and left ventricular function were significantly reduced in the MI animals. Compared with MI alone and MI + cell-free patch groups, the animals received MI + ESC-seeded patches significantly improved blood pressure and ventricular function. The survival rate of the MI mice grafted with MI + ESC-seeded patches was markedly higher than that in MI alone or MI + cell-free patch animals. GFP-positive tissue was detected in infarcted area with grafting of ESC-seeded patch, which suggests the survivors of ESCs and possible myocardial regeneration. Our data demonstrate that grafting of ESC-seeded bioabsorbable patch can repair infarcted myocardium and improve cardiac function in MI mice. This novel approach of combining stem cells and biodegradable materials may provide a therapeutic modality for repairing injured heart.

Key words: Myocardial infarction;Embryonic stem cell;Scaffold;Patch;Cardiac repair

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引用本文：

可庆恩, 杨寅柯, Rana J S, 陈玉, Morgan J P, 萧永福. 培养于生物降解支架膜内的胚胎干细胞可修复小鼠的梗塞心肌 [J]. 生理学报 2005; 57 (6): .

Ke Qingen, Yang Yinke, Rana J S, Chen Yu, Morgan J P, Xiao Yongfu. Embryonic stem cells cultured in biodegradable scaffold repair infarcted myocardium in mice. Acta Physiol Sin 2005; 57 (6): (in Chinese with English abstract).