Recovery of hibernating myocardium using stem cell patch with coronary bypass surgery.

Recovery of hibernating myocardium using stem cell patch with coronary bypass surgery.
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使用干细胞补片和冠状动脉搭桥手术恢复冬眠心肌。

DOI:
10.1016/j.jtcvs.2019.12.073
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发表时间:
2021
期刊:
The Journal of thoracic and cardiovascular surgery
影响因子:
--
通讯作者:
Kelly,RosemaryF
Kelly,RosemaryF
中科院分区:
--
文献类型:
--
作者:
HocumStone,LauraL;Swingen,Cory;Wright,Christin;Qi,StevenS;Rassette,Matt;McFalls,EdwardO;Kelly,RosemaryF

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目的探讨间充质干细胞(MSCs)作为心外膜补片在冠状动脉旁路移植术(CABG)中靶向冬眠心肌(心肌功能持续下降的组织)的作用。12周后,采用左胸内动脉和左前降支移植行单支冠状动脉搭桥术。在CABG期间,在冬眠心肌区应用心外膜补片,其中包括种植在聚乳酸网上的MSCs(n=6),或不含MSCs的假聚乳酸网(n=8.6)。结果CABG+MSC心肌在正性肌力刺激下收缩功能(78.24%±919.6%)较对照组(39.17%±55.57%)明显改善(P<P<0.05)。与假手术对照组相比,CABG+MSC心肌的电子显微镜显示线粒体的大小、数量和形态有所改善;蛋白质分析同样显示线粒体生物发生标记过氧化体增殖物激活受体共激活因子1-α(0.0022±0.0009比0.023±0.009)以及电子传递链的关键成分包括琥珀酸脱氢酶(复合体II)(0.06±0.02比0.14±0.03)的表达增加(P<和三磷酸腺苷合成酶(复合体V)(2.7±0.04vs 4.2±0.26)(P<0.05)。结论在冬眠心肌中,冠状动脉旁路移植术中放置干细胞补片可通过改善线粒体形态和功能来改善心肌功能。
ObjectiveThis study aims to investigate the utility of mesenchymal stem cells (MSCs) applied as an epicardial patch during coronary artery bypass graft (CABG) to target hibernating myocardium; that is, tissue with persistently decreased myocardial function, in a large animal model.MethodsHibernating myocardium was induced in juvenile swine (n = 12) using a surgically placed constrictor on the left anterior descending artery, causing stenosis without infarction. After 12 weeks, single-vessel CABG was performed using left internal thoracic artery to left anterior descending artery graft. During CABG, an epicardial patch was applied to the hibernating myocardium region consisting either of MSCs grown onto a polyglactin mesh (n = 6), or sham polyglactin mesh without MSCs (n = 6). Four weeks after CABG and patch placement, cardiac magnetic resonance imaging was performed and cardiac tissue was examined by gross inspection, including coronary dilators for vessel stenosis and patency, electron microscopy, protein assays, and proteomic analysis.ResultsCABG + MSC myocardium showed improvement in contractile function (78.24% ± 19.6%) compared with sham patch (39.17% ± 5.57%) during inotropic stimulation (P< .05). Compared with sham patch control, electron microscopy of CABG + MSC myocardium showed improvement in mitochondrial size, number, and morphology; protein analysis similarly showed increases in expression of the mitochondrial biogenesis marker peroxisome proliferator-activated receptor gamma coactivator 1-alpha (0.0022 ± 0.0009 vs 0.023 ± 0.009) (P< .01) along with key components of the electron transport chain, including succinate dehydrogenase (complex II) (0.06 ± 0.02 vs 0.14 ± 0.03) (P< .05) and adenosine triphosphate synthase (complex V) (2.7 ± 0.4 vs 4.2 ± 0.26) (P< .05).ConclusionsIn hibernating myocardium, placement of a stem cell patch during CABG shows promise in improving myocardial function by improving mitochondrial morphology and function.
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