Sheu Jiunn-Jye, Yeh Jui-Ning, Chen Yin-Chia, Chiang John Y, Sung Pei-Hsun, Huang Chi-Ruei, Li Yi-Chen, Yip Hon-Kan
Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC.
Int J Surg. 2024 Dec 1;110(12):7546-7562. doi: 10.1097/JS9.0000000000002119.
We investigated whether shock wave (SW)-pretreated autologous adipocyte-derived mesenchymal stem cells (ADMSCs) seeded in the cell-sheet scaffold (CSS) could inhibit left ventricular (LV) remodeling and improve LV ejection fraction (LVEF) in old myocardial infarction (MI).
Mini-pigs ( n =20) were divided into group 1 (sham-operated control), group 2 (old MI), group 3 (old MI + autologous ADMSCs/1.0×10 7 in CSS on LV myocardium), and group 4 [old MI + SW (0.12 mJ/mm 2 for total 140 shots)-pretreated ADMSCs in CSS on LV myocardium]. Treatments started on day 28 after MI induction. In-vivo and in-vitro studies were conducted.
Cell viability/relative mitochondria DNA expression/mitochondrial cytochrome C/adenosine triphosphate concentration in ADMCSs and protein expressions of angiogenesis factors [vascular endothelial growth factor (VEGF)/stromal cell-derived factor-1 (SDF-1)/mitochondrial respiratory chain complexes I-IV/oxygen consumption rate] were higher in group 4 than in group 3 ( P <0.001). By day 180, LVEF and small vessel numbers in the peri-infarct or infarct area were highest in group 1, lowest in group 2, and significantly lower in group 3 than in group 4. In contrast, the LV dimension was opposite to the pattern of change in LVEF in all groups ( P <0.0001). The basal/middle/apical infarct and fibrotic areas were inversely related to LVEF in all groups (all P <0.0001). Protein levels of angiogenetic markers (SDF-1α/C-X-C chemokine receptor type 4/VEGF/angiopoietin-1) were significantly and persistently increased from groups 1 to 4. In contrast, protein levels of endothelial cell markers (von Willebrand factor or endothelial nitric oxide synthase) showed an identical pattern to LVEF in all groups (all P <0.0001).
SW pretreatment of ADMSCs seeded in CSS offered significant benefits in preserving LV performance and ameliorating LV remodeling in mini-pigs with old MI.
我们研究了接种于细胞片支架（CSS）中的经冲击波（SW）预处理的自体脂肪来源间充质干细胞（ADMSC）是否能抑制老年心肌梗死（MI）中的左心室（LV）重构并提高左心室射血分数（LVEF）。
将小型猪（n = 20）分为1组（假手术对照组）、2组（老年MI组）、3组（老年MI + 将1.0×10⁷个自体ADMSC接种于左心室心肌的CSS组）和4组[老年MI + 将经SW（0.12 mJ/mm²，共140次冲击）预处理的ADMSC接种于左心室心肌的CSS组]。在MI诱导后第28天开始治疗。进行了体内和体外研究。
4组ADMSC中的细胞活力/相对线粒体DNA表达/线粒体细胞色素C/三磷酸腺苷浓度以及血管生成因子的蛋白表达[血管内皮生长因子（VEGF）/基质细胞衍生因子-1（SDF-1）/线粒体呼吸链复合物I-IV/耗氧率]均高于3组（P < 0.001）。到第180天时，1组的LVEF和梗死周边或梗死区域的小血管数量最高，2组最低，3组明显低于4组。相反，所有组的左心室尺寸与LVEF的变化模式相反（P < 0.0001）。所有组的基底/中间/心尖梗死和纤维化面积与LVEF呈负相关（均P < 0.0001）。从1组到4组，血管生成标志物（SDF-1α/C-X-C趋化因子受体4型/VEGF/血管生成素-1）的蛋白水平显著且持续升高。相反，内皮细胞标志物（血管性血友病因子或内皮型一氧化氮合酶）的蛋白水平在所有组中与LVEF呈现相同模式（均P < 0.0001）。
接种于CSS中的经SW预处理的ADMSC在维持老年MI小型猪的左心室功能和改善左心室重构方面具有显著益处。
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