Valina Christian, Pinkernell Kai, Song Yao-Hua, Bai Xiaowen, Sadat Sanga, Campeau Richard J, Le Jemtel Thierry H, Alt Eckhard
Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Eur Heart J. 2007 Nov;28(21):2667-77. doi: 10.1093/eurheartj/ehm426. Epub 2007 Oct 11.
This study was designed to assess whether intracoronary application of adipose tissue-derived stem cells (ADSCs) compared with bone marrow-derived stem cells (BMSCs) and control could improve cardiac function after 30 days in a porcine acute myocardial infarction/reperfusion model.
An acute transmural porcine myocardial infarction was induced by inflating an angioplasty balloon for 180 min in the mid-left anterior descending artery. Two million cultured autologous stem cells were intracoronary injected through the central lumen of the inflated balloon catheter. Analysis of scintigraphic data obtained after 28 +/- 3 days showed that both absolute and relative perfusion defect decreased significantly after intracoronary administration of ADSCs or BMSCs (relative 30 or 31%, respectively), compared with carrier administration alone (12%, P = 0.048). Left ventricular ejection fraction after 4 weeks increased significantly more after ADSC and BMSC administration than after carrier administration: 11.39 +/- 4.62 and 9.59 +/- 7.95%, respectively vs. 1.95 +/- 4.7%, P = 0.02). The relative thickness of the ventricular wall in the infarction area after cell administration was significantly greater than that after carrier administration. The vascular density of the border zone also improved. The grafted cells co-localized with von Willebrand factor and alpha-smooth muscle actin and incorporated into newly formed vessels.
This is the first study to show that not only bone marrow-derived cells but also ADSCs engrafted in the infarct region 4 weeks after intracoronary cell transplantation and improved cardiac function and perfusion via angiogenesis.
本研究旨在评估在猪急性心肌梗死/再灌注模型中,与骨髓来源的干细胞(BMSCs)及对照组相比,冠状动脉内应用脂肪组织来源的干细胞(ADSCs)能否在30天后改善心脏功能。
通过在左前降支中段充盈血管成形术球囊180分钟诱导急性透壁性猪心肌梗死。将200万培养的自体干细胞通过充盈球囊导管的中心腔进行冠状动脉内注射。对28±3天后获得的闪烁扫描数据进行分析显示,与单独给予载体相比(12%,P = 0.048),冠状动脉内给予ADSCs或BMSCs后,绝对和相对灌注缺损均显著降低(分别为30%或31%)。4周后,给予ADSCs和BMSCs后的左心室射血分数较给予载体后显著增加:分别为11.39±4.62%和9.59±7.95%,而给予载体后为1.95±4.7%,P = 0.02)。细胞给药后梗死区域心室壁的相对厚度显著大于载体给药后。边缘区的血管密度也有所改善。移植的细胞与血管性血友病因子和α-平滑肌肌动蛋白共定位,并整合到新形成的血管中。
这是第一项表明冠状动脉内细胞移植4周后,不仅骨髓来源的细胞,而且ADSCs也能植入梗死区域并通过血管生成改善心脏功能和灌注的研究。