Moelker Amber D, Baks Timo, Wever Kim M A M, Spitskovsky Dimitry, Wielopolski Piotr A, van Beusekom Heleen M M, van Geuns Robert-Jan, Wnendt Stephan, Duncker Dirk J, van der Giessen Wim J
Cardiology, Thoraxcenter, Erasmus MC Rotterdam, Rotterdam, The Netherlands.
J Mol Cell Cardiol. 2007 Apr;42(4):735-45. doi: 10.1016/j.yjmcc.2007.01.005. Epub 2007 Jan 18.
Regeneration of infarcted myocardium by injecting stem cells has been proposed to prevent heart failure. We studied the i.c. administration of human umbilical cord blood stem cells (USSC) in a porcine model of myocardial infarction (MI) and reperfusion. In 15 swine, MI was induced by balloon-occlusion of the left circumflex coronary artery (LCX) for 2 h followed by reperfusion. Five swine served as healthy controls. One week later, magnetic resonance imaging (MRI) was performed to assess left ventricular (LV) function and infarct size. Then, under immune suppression, 6 of the 12 surviving MI swine received intracoronary injection of approximately 10(8) human USSC in the LCX while the other MI-swine received medium. Four weeks later all swine underwent follow-up MRI, and were sacrificed for histology. One week after MI, end-diastolic volume (92+/-3 mL) and LV mass (75+/-2 g) were larger, while ejection fraction (42+/-2%) was smaller than in healthy control (68+/-3 mL, 66+/-3 g and 55+/-3%, all P<0.05). Regional wall thickening (-7+/-2%) in the LCX area became akinetic. No difference in global and regional LV function at 5 weeks was observed between MI animals receiving USSC or medium. Infarct size after USSC treatment was significantly larger (20+/-3 g vs. 8+/-2 g, P<0.05). USSC survived only in the infarct border zone at 5 weeks and did not express cardiomyocyte or endothelial markers. Histology showed that intracoronary injection of USSC caused micro infarctions by obstructing blood vessels. In swine with a 1 week old MI, injection of USSC via the intracoronary route does not improve LV function 4 weeks later.
通过注射干细胞使梗死心肌再生已被提议用于预防心力衰竭。我们研究了在猪心肌梗死(MI)和再灌注模型中经冠状动脉内给予人脐带血干细胞(USSC)的情况。在15头猪中,通过球囊闭塞左旋冠状动脉(LCX)2小时诱导MI,随后进行再灌注。5头猪作为健康对照。一周后,进行磁共振成像(MRI)以评估左心室(LV)功能和梗死面积。然后,在免疫抑制下,12头存活的MI猪中的6头在LCX内接受冠状动脉内注射约10⁸个人USSC,而其他MI猪接受培养基。四周后,所有猪均接受随访MRI检查,并处死后进行组织学检查。MI后一周,舒张末期容积(92±3 mL)和LV质量(75±2 g)增大,而射血分数(42±2%)小于健康对照(68±3 mL、66±3 g和55±3%,所有P<0.05)。LCX区域的局部室壁增厚(-7±2%)变为运动不能。接受USSC或培养基的MI动物在5周时的整体和局部LV功能无差异。USSC治疗后的梗死面积显著更大(20±3 g对8±2 g,P<0.05)。5周时USSC仅存活于梗死边缘区,且不表达心肌细胞或内皮标志物。组织学显示冠状动脉内注射USSC通过阻塞血管导致微梗死。在患有1周龄MI的猪中,经冠状动脉途径注射USSC在4周后并未改善LV功能。