Molina Ezequiel J, Palma Jon, Gupta Dipin, Torres Denise, Gaughan John P, Houser Steven, Macha Mahender
Division of Cardiac and Thoracic Surgery, Temple University School of Medicine, Philadelphia, PA, USA.
J Thorac Cardiovasc Surg. 2008 Feb;135(2):292-9, 299.e1. doi: 10.1016/j.jtcvs.2007.10.003. Epub 2007 Dec 26.
In a rat model of pressure overload hypertrophy, we studied the effects of intracoronary delivery of mesenchymal stem cells on hemodynamic performance, exercise capacity, systemic inflammation, and left ventricular reverse remodeling.
Sprague-Dawley rats underwent aortic banding and were followed up by echocardiographic scanning. After a decrease in fractional shortening of 25% from baseline, animals were randomized to intracoronary injection of mesenchymal stem cells (MSC group; n = 28) or phosphate-buffered saline solution (control group; n = 20). Hemodynamic and echocardiographic assessment, swim testing to exhaustion, and measurement of inflammatory markers were performed before the rats were humanely killed on postoperative day 7, 14, 21, or 28.
Injection of mesenchymal stem cells improved systolic function in the MSC group compared with the control group (mean +/- standard deviation: maximum dP/dt 3048 +/- 230 mm Hg/s vs 2169 +/- 97 mm Hg/s at 21 days and 3573 +/- 741 mm Hg/s vs 1363 +/- 322 mm Hg/s at 28 days: P < .001). Time to exhaustion was similarly increased in the MSC group compared with controls (487 +/- 35 seconds vs 306 +/- 27 seconds at 28 days; P < .01). Serum levels of interleukins 1 and 6, tumor necrosis factor-alpha, and brain natriuretic peptide-32 were significantly decreased in animals treated with mesenchymal stem cells. Stem cell transplantation improved left ventricular fractional shortening at 21 and 28 days. Left ventricular end-systolic and end-diastolic diameters were also improved at 28 days.
In this model of pressure overload hypertrophy, intracoronary delivery of mesenchymal stem cells during heart failure was associated with an improvement in hemodynamic performance, maximal exercise tolerance, systemic inflammation, and left ventricular reverse remodeling. This study suggests a potential role of this treatment strategy for the management of hypertrophic heart failure resulting from pressure overload.
在压力超负荷肥大的大鼠模型中,我们研究了冠状动脉内递送间充质干细胞对血流动力学性能、运动能力、全身炎症和左心室逆向重构的影响。
对Sprague-Dawley大鼠进行主动脉缩窄,并通过超声心动图扫描进行随访。在射血分数从基线下降25%后,将动物随机分为冠状动脉内注射间充质干细胞(MSC组;n = 28)或磷酸盐缓冲盐水溶液(对照组;n = 20)。在术后第7、14、21或28天对大鼠实施安乐死之前,进行血流动力学和超声心动图评估、游泳耐力测试以及炎症标志物测量。
与对照组相比,MSC组注射间充质干细胞改善了收缩功能(平均值±标准差:21天时最大dP/dt为3048±230 mmHg/s,对照组为2169±97 mmHg/s;28天时为3573±741 mmHg/s,对照组为1363±322 mmHg/s:P <.001)。与对照组相比,MSC组的耐力时间同样增加(28天时为487±35秒,对照组为306±27秒;P <.01)。间充质干细胞治疗的动物血清白细胞介素1和6、肿瘤坏死因子-α以及脑钠肽-32水平显著降低。干细胞移植在21天和28天时改善了左心室射血分数。28天时左心室收缩末期和舒张末期直径也有所改善。
在这个压力超负荷肥大模型中,心力衰竭期间冠状动脉内递送间充质干细胞与血流动力学性能、最大运动耐量、全身炎症和左心室逆向重构的改善相关。这项研究表明这种治疗策略在管理由压力超负荷导致的肥厚性心力衰竭方面具有潜在作用。