Minneapolis VA Health Care System, Minneapolis, Minn; Department of Surgery, University of Minnesota, Minneapolis, Minn.
Department of Surgery, University of Minnesota, Minneapolis, Minn.
J Thorac Cardiovasc Surg. 2021 Jul;162(1):e3-e16. doi: 10.1016/j.jtcvs.2019.12.073. Epub 2020 Jan 11.
This 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.
Hibernating 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.
CABG + 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).
In hibernating myocardium, placement of a stem cell patch during CABG shows promise in improving myocardial function by improving mitochondrial morphology and function.
本研究旨在探讨在冠状动脉旁路移植术（CABG）中应用间充质干细胞（MSCs）作为心外膜贴片治疗冬眠心肌的效果。冬眠心肌是指心肌功能持续下降的组织，我们采用在左前降支放置缩窄器的手术方法在幼年猪模型中诱导产生了冬眠心肌。12 周后，通过左内乳动脉至左前降支的单支血管 CABG 手术，将左前降支的狭窄病变充分血运重建。在 CABG 过程中，我们将 MSCs 种植在聚甘醇酸网片上的心外膜贴片（MSC 组，n=6）或没有种植 MSCs 的 sham 聚甘醇酸网片（sham 组，n=6）应用于冬眠心肌区域。CABG 和贴片放置 4 周后，进行心脏磁共振成像检查，并通过大体检查、包括用于评估血管狭窄和通畅性的冠状动脉扩张剂、电子显微镜、蛋白质检测和蛋白质组分析等方法检查心脏组织。
在正性肌力刺激下，与 sham 贴片相比，CABG+MSC 心肌的收缩功能得到改善（78.24%±19.6% 比 39.17%±5.57%，P<.05）。与 sham 贴片对照组相比，CABG+MSC 心肌的电子显微镜检查显示线粒体大小、数量和形态得到改善；蛋白质分析同样显示线粒体生物发生标志物过氧化物酶体增殖物激活受体γ共激活因子 1-α（0.0022±0.0009 比 0.023±0.009）（P<.01）和电子传递链的关键组成部分，包括琥珀酸脱氢酶（复合物 II）（0.06±0.02 比 0.14±0.03）（P<.05）和三磷酸腺苷合酶（复合物 V）（2.7±0.4 比 4.2±0.26）（P<.05）的表达增加。
在冬眠心肌中，CABG 期间放置干细胞贴片有望通过改善线粒体形态和功能来改善心肌功能。
