Postinfarct intramyocardial injection of mesenchymal stem cells pretreated with TGF-alpha improves acute myocardial function.
Postinfarct intramyocardial injection of mesenchymal stem cells pretreated with TGF-alpha improves acute myocardial function.
复制标题
DOI：
10.1152/ajpregu.00084.2010
复制
发表时间：
2010-07
期刊：
影响因子：
--
通讯作者：
J. Herrmann;A. Abarbanell;Brent R. Weil;Yue Wang;Jeffrey A. Poynter;Mariuxi C. Manukyan;D. Meldrum
中科院分区：
文献类型：
--
作者：
J. Herrmann;A. Abarbanell;Brent R. Weil;Yue Wang;Jeffrey A. Poynter;Mariuxi C. Manukyan;D. Meldrum
干细胞治疗为心肌梗死(MI)提供了有希望的潜力，但损伤后释放的内源性分子可能会损害移植后的干细胞功能。干细胞介导的心脏保护在一定程度上是通过旁分泌作用实现的，转化生长因子-α(TGF-α)已被证明可以增强旁分泌功能。然而，尚不清楚用转化生长因子-α预处理干细胞是否能增加急性心肌梗死后干细胞介导的心脏保护作用。用转化生长因子-α(250 ng/ml)处理间充质干细胞(MSCs)24 h，分离成年雄性SD大鼠心脏，用Langendorff方法灌流。结扎冠状动脉左前降支诱导心肌梗死。结扎后30min，在梗死区注射赋形剂或1×10(6)骨髓间充质干细胞(含或不含预处理)，心脏再灌流60min。连续测定左心功能，伊文思蓝染色和2，3，5-三苯基四氮唑染色评价心肌梗死面积。检测心肌细胞产生IL-1β、IL-6及caspase 3活性。冠状动脉结扎后左心功能显着下降，注射未经处理的MSCs后左心功能明显改善，注射经处理的MSCs后左心功能改善的程度更大。此外，心肌梗死面积、心肌caspase3活性和IL-6的产生在注射预处理细胞的心脏中最低。急性心肌梗死后心肌内注射经转化生长因子-α处理的骨髓间充质干细胞可增加心肌功能，减轻心肌损伤。这一策略可能有助于优化干细胞治疗急性心肌梗死的疗效。
Stem cell-based therapies offer promising potential for myocardial infarction (MI), but endogenous molecules released in response to injury likely impair posttransplantation stem cell function. Stem cell-mediated cardioprotection occurs in part via paracrine effects, and transforming growth factor-alpha (TGF-alpha) has been shown to enhance paracrine function. However, it is unknown whether pretreating stem cells with TGF-alpha increases stem cell-mediated cardioprotection after acute MI. Mesenchymal stem cells (MSCs) were treated with TGF-alpha (250 ng/ml) for 24 h. Adult male Sprague-Dawley rat hearts were isolated and perfused using the Langendorff method. MI was induced by ligating the left anterior descending coronary artery. Postligation (30 min), vehicle or 1 x 10(6) MSCs with or without pretreatment were injected in the infarct border zones, and the hearts were perfused for an additional 60 min. Left ventricular function was continuously measured, and infarct size was assessed with Evans blue dye and 2,3,5-triphenyltetrazolium chloride staining. Myocardial production of interleukin (IL)-1beta and IL-6 and caspase 3 activation was also measured. Left ventricular function decreased significantly following coronary artery ligation but improved following injection of untreated MSCs and to a greater extent after injection of pretreated MSCs. In addition, the infarct area, myocardial caspase 3 activation, and IL-6 production were lowest in hearts injected with pretreated cells. Intramyocardial injection of TGF-alpha-pretreated MSCs after acute MI is associated with increased myocardial function and decreased myocardial injury. This strategy may be useful for optimizing the therapeutic efficacy of stem cells for the treatment of acute MI.