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心肌内移植人脂肪来源的基质细胞和内皮祖细胞混合物在改善心肌梗死后大鼠左心室功能方面并不优于单独细胞类型移植。

Intramyocardial transplantation of human adipose-derived stromal cell and endothelial progenitor cell mixture was not superior to individual cell type transplantation in improving left ventricular function in rats with myocardial infarction.

机构信息

Department of Cardiology, Korea University Anam Hospital, Seoul, Republic of Korea.

出版信息

Int J Cardiol. 2013 Apr 5;164(2):205-11. doi: 10.1016/j.ijcard.2011.06.128. Epub 2011 Jul 26.

Abstract

BACKGROUND

Both adipose-derived stromal cells (ASCs) and endothelial progenitor cells (EPCs) have high potential for promoting tissue revascularization and functional recovery in acute myocardial infarction (AMI) models. We investigated the functional effects of intramyocardial transplantation of a human ASC and EPC mixture in immunodeficient rats after MI.

METHODS

MI was induced by ligating left anterior descending coronary artery. Survived rats were randomly assigned to 1 of 4 different groups: the control group (n=10, saline in 100μL), the ASC group (n=10, 10(6) ASCs), the EPC group (n=10, 10(6) EPCs), or the ASC+EPC group (n=10, 2×10(5) ASCs+8×10(5) EPCs). Left ventricular (LV) function was compared using echocardiography during the 28-day follow-up. GAP43+ nerve sprouting and smooth muscle α-actin+angiogenesis were also compared.

RESULTS

Serial changes in LV ejection fraction (EF) and fractional shortening revealed significant increases in the ASC, EPC, and ASC+EPC groups when compared to the control group during the follow-up (49±3%, 49±4%, 47±4%, 39±2%, P<0.001, respectively for LVEF) (33±4%, 32±2%, 31±2%, 23±2%, P=0.002, respectively for fractional shortening). The number of α-actin+arterioles and GAP43+ nerve area was significantly greater in the ASC, EPC, and ASC+EPC groups when compared to the control group in the peri-infarct area (34.4±1.0/mm(2), 35.9±1.1/mm(2), 35.3±0.9/mm(2), 17.4±0.7/mm(2), P<0.001, respectively for angiogenesis) (346.2±10.7μm(2)/mm(2), 357.2±12.8μm(2)/mm(2), 368.0±9.7μm(2)/mm(2), 174.6±7.9μm(2)/mm(2), P<0.001, respectively for nerve sprouting).

CONCLUSIONS

[corrected] Intramyocardial injections of ASCs, EPCs, or ASCs+EPCs are effective modalities for the treatment of myocardial damage in rats and may expand the potential clinical application of ASC or EPC therapy in patients with ischemic heart disease.

摘要

背景

脂肪来源的基质细胞(ASCs)和内皮祖细胞(EPCs)都具有促进急性心肌梗死(AMI)模型组织再血管化和功能恢复的巨大潜力。我们研究了在 MI 后免疫缺陷大鼠心肌内移植人 ASC 和 EPC 混合物的功能影响。

方法

通过结扎左前降支冠状动脉诱导 MI。存活的大鼠被随机分配到 4 个不同组中的 1 个:对照组(n=10,100μL 生理盐水)、ASC 组(n=10,10(6)ASCs)、EPC 组(n=10,10(6)EPCs)或 ASC+EPC 组(n=10,2×10(5)ASCs+8×10(5)EPCs)。在 28 天的随访期间,使用超声心动图比较左心室(LV)功能。还比较了 GAP43+神经发芽和平滑肌α-肌动蛋白+血管生成。

结果

LV 射血分数(EF)和短轴缩短率的连续变化表明,在随访期间,与对照组相比,ASC、EPC 和 ASC+EPC 组均有显著增加(49±3%、49±4%、47±4%、39±2%,P<0.001,分别为 LVEF)(33±4%、32±2%、31±2%、23±2%,P=0.002,分别为短轴缩短率)。与对照组相比,在梗死周围区域,α-肌动蛋白+小动脉和 GAP43+神经区域的数量在 ASC、EPC 和 ASC+EPC 组中均显著增加(34.4±1.0/mm(2)、35.9±1.1/mm(2)、35.3±0.9/mm(2)、17.4±0.7/mm(2),P<0.001,分别为血管生成)(346.2±10.7μm(2)/mm(2)、357.2±12.8μm(2)/mm(2)、368.0±9.7μm(2)/mm(2)、174.6±7.9μm(2)/mm(2),P<0.001,分别为神经发芽)。

结论

心肌内注射 ASC、EPC 或 ASC+EPC 是治疗大鼠心肌损伤的有效方法,可能扩大 ASC 或 EPC 治疗缺血性心脏病患者的潜在临床应用。

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