Intravenous infusion of bone marrow mesenchymal stem cells improves myocardial function in a rat model of myocardial ischemia*
Intravenous infusion of bone marrow mesenchymal stem cells improves myocardial function in a rat model of myocardial ischemia*
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DOI：
10.1097/01.ccm.0000285992.99391.7e
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发表时间：
2007-11
影响因子：
8.8
通讯作者：
Tong Wang;Wanchun Tang;Shijie Sun;G. Ristagno;Zitong Huang;M. Weil
中科院分区：
文献类型：
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作者：
Tong Wang;Wanchun Tang;Shijie Sun;G. Ristagno;Zitong Huang;M. Weil
目的：探讨骨髓间充质干细胞（MSCs）在大鼠心肌缺血模型中三个不同部位的传递作用。设计：前瞻性、随机、对照研究。单位：学校附属研究所。实验对象：雄性sd大鼠。干预措施：在全身麻醉下进行开胸手术。结扎左冠状动脉前降支诱导心肌缺血。1个月后，动物随机接受5 × 106个PKH26标记的MSCs，磷酸盐缓冲液或单独磷酸盐缓冲液作为安慰剂注射至右股静脉，直接进入左室（LV）腔，或前室游离壁缺血区。测量和主要结果：超声心动图测量心肌功能，包括射血分数和分数缩短，在给予MSCs或磷酸盐缓冲液后2周和4周进行定量。在给予MSCs或磷酸盐缓冲液4周后测量血液动力学，包括心脏指数、左室dP/dt40、左室阴性dP/dt和左室舒张压。从每个收获的心脏用低温恒温器获得5米切片，对MSCs进行计数。注射MSCs后，无论注射部位如何，射血分数、分数缩短、心脏指数、左室dP/dt40、左室负dP/dt和左室舒张压均有显著改善。而直接注射心肌后，心肌切片中MSCs计数明显增多。结论：与注射部位无关，也与心肌中骨髓间充质干细胞的浓度不同，MSCs治疗各组动物的心肌功能均得到了相当程度的改善。
Objective:We investigated the effects of three different sites for delivery of bone marrow mesenchymal stem cells (MSCs) in a rat model of myocardial ischemia. Design:Prospective, randomized, controlled study. Setting:University affiliated research institute. Subjects:Male Sprague-Dawley rats. Interventions:A thoracotomy was performed under general anesthesia. Myocardial ischemia was induced by ligation of the left anterior descending coronary artery. One month later, animals were randomized to receive 5 × 106 MSCs labeled with PKH26 in phosphate buffer solution or phosphate buffer solution alone as a placebo by injection into right femoral vein, directly into the left ventricular (LV) cavity, or into the ischemic zone in the anterior ventricular free wall. Measurements and Main Results:Echocardiographically measured myocardial function, including ejection fraction and fractional shortening, was quantitated 2 wks and 4 wks after administering MSCs or phosphate buffer solution. Hemodynamics, including cardiac index, LV dP/dt40, LV negative dP/dt, and LV diastolic pressure were measured 4 wks after administering MSCs or phosphate buffer solution. MSCs were counted in 5-m sections obtained with cryostat from each harvested heart. Significant improvements in ejection fraction, fractional shortening, cardiac index, LV dP/dt40, LV negative dP/dt, and LV diastolic pressure followed injection of MSCs, regardless of the site of injection. However, the number of MSCs counted in the heart sections was significantly greater after direct myocardial injection. Conclusions:Independently of the site of injection and regardless of the different concentration of bone marrow mesenchymal stem cells identified in the myocardium, myocardial function was comparably improved in all groups of animals treated with MSCs.