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直接植入与富血小板纤维蛋白包埋的脂肪间充质干细胞治疗大鼠急性心肌梗死的比较

Direct implantation versus platelet-rich fibrin-embedded adipose-derived mesenchymal stem cells in treating rat acute myocardial infarction.

作者信息

Sun Cheuk-Kwan, Zhen Yen-Yi, Leu Steve, Tsai Tzu-Hsien, Chang Li-Teh, Sheu Jiunn-Jye, Chen Yung-Lung, Chua Sarah, Chai Han-Tan, Lu Hung-I, Chang Hsueh-Wen, Lee Fan-Yen, Yip Hon-Kan

机构信息

Department of Emergency Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.

Division of Cardiology, Department of Internal Medicine, Taiwan.

出版信息

Int J Cardiol. 2014 May 15;173(3):410-23. doi: 10.1016/j.ijcard.2014.03.015. Epub 2014 Mar 14.

Abstract

BACKGROUND

This study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation.

METHODS

Twenty-eight male adult Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI only), group 3 (AMI+direct ADMSC implantation), and group 4 (AMI+PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI.

RESULTS

LV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p<0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p<0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31+, CXCR4+, SDF-1α+), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit+, Sca-1+) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p<0.005).

CONCLUSION

PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling.

摘要

背景

本研究旨在测试在大鼠左冠状动脉前降支(LAD)结扎所致急性心肌梗死(AMI)模型中,嵌入富血小板纤维蛋白(PRF)支架的脂肪源性间充质干细胞(ADMSC)在改善左心室(LV)功能和减少LV重构方面是否优于直接植入ADMSC。

方法

28只成年雄性Sprague Dawley大鼠平均分为1组[假手术对照组]、2组(仅AMI组)、3组(AMI+直接植入ADMSC组)和4组(AMI+PRF包埋自体ADMSC组),于AMI后第42天处死。

结果

LV收缩和舒张尺寸及容积、梗死/纤维化面积在2组最高,1组最低,3组显著高于4组,而LV功能和LV缩短分数呈现相反模式(p<0.005)。炎症(氧化应激、IL-1β、MMP-9)、凋亡(线粒体Bax、裂解的PARP)、纤维化(Smad3、TGF-β)和压力过载生物标志物(BNP、MHC-β)的蛋白表达呈现与LV尺寸相似的模式,而抗炎(IL-10)、抗凋亡(Bcl-2)和抗纤维化(Smad1/5、BMP-2)指标在四组中呈现与LV功能相似的模式(均p<0.05)。梗死心肌中蛋白(CXCR4、SDF-1α、VEGF)、细胞(CD31+、CXCR4+、SDF-1α+)和免疫组化(小血管)水平的血管生成生物标志物以及心脏干细胞标志物(C-kit+、Sca-1+)在4组最高,1组最低,3组显著高于2组(均p<0.005)。

结论

PRF包埋的ADMSC在保留LV功能和减轻LV重构方面优于直接植入ADMSC。

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