Dawn Buddhadeb, Stein Adam B, Urbanek Konrad, Rota Marcello, Whang Brian, Rastaldo Raffaella, Torella Daniele, Tang Xian-Liang, Rezazadeh Arash, Kajstura Jan, Leri Annarosa, Hunt Greg, Varma Jai, Prabhu Sumanth D, Anversa Piero, Bolli Roberto
Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40202, USA.
Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3766-71. doi: 10.1073/pnas.0405957102. Epub 2005 Feb 25.
The ability of cardiac stem cells (CSCs) to promote myocardial repair under clinically relevant conditions (i.e., when delivered intravascularly after reperfusion) is unknown. Thus, rats were subjected to a 90-min coronary occlusion; at 4 h after reperfusion, CSCs were delivered to the coronary arteries via a catheter positioned into the aortic root. Echocardiographic analysis showed that injection of CSCs attenuated the increase in left ventricular (LV) end-diastolic dimensions and impairment in LV systolic performance at 5 weeks after myocardial infarction. Pathologic analysis showed that treated hearts exhibited a smaller increase in LV chamber diameter and volume and a higher wall thickness-to-chamber radius ratio and LV mass-to-chamber volume ratio. CSCs induced myocardial regeneration, decreasing infarct size by 29%. A diploid DNA content and only two chromosomes 12 were found in new cardiomyocytes, indicating that cell fusion did not contribute to tissue reconstitution. In conclusion, intravascular injection of CSCs after reperfusion limits infarct size, attenuates LV remodeling, and ameliorates LV function. This study demonstrates that CSCs are effective when delivered in a clinically relevant manner, a clear prerequisite for clinical translation, and that these beneficial effects are independent of cell fusion. The results establish CSCs as candidates for cardiac regeneration and support an approach in which the heart's own stem cells could be collected, expanded, and stored for subsequent therapeutic repair.
心脏干细胞（CSCs）在临床相关条件下（即再灌注后经血管内递送时）促进心肌修复的能力尚不清楚。因此，对大鼠进行90分钟的冠状动脉闭塞；再灌注后4小时，通过置于主动脉根部的导管将CSCs递送至冠状动脉。超声心动图分析显示，注射CSCs可减轻心肌梗死后5周时左心室（LV）舒张末期内径的增加以及LV收缩功能的损害。病理分析表明，治疗后的心脏LV腔直径和容积增加较小，壁厚与腔半径比以及LV质量与腔容积比更高。CSCs诱导心肌再生，使梗死面积减少29%。在新的心肌细胞中发现二倍体DNA含量且仅有两条12号染色体，表明细胞融合对组织重构没有贡献。总之，再灌注后经血管内注射CSCs可限制梗死面积，减轻LV重构，并改善LV功能。本研究表明，以临床相关方式递送CSCs是有效的，这是临床转化的明确前提条件，并且这些有益作用独立于细胞融合。这些结果确立了CSCs作为心脏再生候选者的地位，并支持一种可以收集、扩增和储存心脏自身干细胞以备后续治疗修复的方法。
