Dawn Buddhadeb, Tiwari Sumit, Kucia Magdalena J, Zuba-Surma Ewa K, Guo Yiru, Sanganalmath Santosh K, Abdel-Latif Ahmed, Hunt Greg, Vincent Robert J, Taher Hisham, Reed Nathan J, Ratajczak Mariusz Z, Bolli Roberto
Institute of Molecular Cardiology, University of Louisville, Louisville, Kentucky 40292, USA.
Stem Cells. 2008 Jun;26(6):1646-55. doi: 10.1634/stemcells.2007-0715. Epub 2008 Apr 17.
Adult bone marrow (BM) contains Sca-1+/Lin-/CD45- very small embryonic-like stem cells (VSELs) that express markers of several lineages, including cardiac markers, and differentiate into cardiomyocytes in vitro. We examined whether BM-derived VSELs promote myocardial repair after a reperfused myocardial infarction (MI). Mice underwent a 30-minute coronary occlusion followed by reperfusion and received intramyocardial injection of vehicle (n= 11), 1 x 10(5) Sca-1+/Lin-/CD45+ enhanced green fluorescent protein (EGFP)-labeled hematopoietic stem cells (n= 13 [cell control group]), or 1 x 10(4) Sca-1+/Lin-/CD45- EGFP-labeled cells (n= 14 [VSEL-treated group]) at 48 hours after MI. At 35 days after MI, VSEL-treated mice exhibited improved global and regional left ventricular (LV) systolic function (echocardiography) and attenuated myocyte hypertrophy in surviving tissue (histology and echocardiography) compared with vehicle-treated controls. In contrast, transplantation of Sca-1+/Lin-/CD45+ cells failed to confer any functional or structural benefits. Scattered EGFP+ myocytes and capillaries were present in the infarct region in VSEL-treated mice, but their numbers were very small. These results indicate that transplantation of a relatively small number of CD45- VSELs is sufficient to improve LV function and alleviate myocyte hypertrophy after MI, supporting the potential therapeutic utility of these cells for cardiac repair. Disclosure of potential conflicts of interest is found at the end of this article.
成人骨髓(BM)中含有Sca-1+/Lin-/CD45- 非常小的胚胎样干细胞(VSELs),这些细胞表达包括心脏标志物在内的多种谱系标志物,并能在体外分化为心肌细胞。我们研究了骨髓来源的VSELs是否能促进再灌注心肌梗死后的心肌修复。小鼠经历30分钟冠状动脉闭塞后再灌注,并在心肌梗死后48小时接受心肌内注射溶剂(n = 11)、1×10(5)个Sca-1+/Lin-/CD45+增强型绿色荧光蛋白(EGFP)标记的造血干细胞(n = 13 [细胞对照组])或1×10(4)个Sca-1+/Lin-/CD45- EGFP标记的细胞(n = 14 [VSEL治疗组])。在心肌梗死后35天,与溶剂治疗的对照组相比,VSEL治疗的小鼠表现出整体和局部左心室(LV)收缩功能改善(超声心动图),存活组织中的心肌细胞肥大减轻(组织学和超声心动图)。相比之下,移植Sca-1+/Lin-/CD45+细胞未能带来任何功能或结构上的益处。在VSEL治疗的小鼠梗死区域存在散在的EGFP+心肌细胞和毛细血管,但其数量非常少。这些结果表明,移植相对少量的CD45- VSELs足以改善心肌梗死后的左心室功能并减轻心肌细胞肥大,支持了这些细胞在心脏修复方面的潜在治疗效用。潜在利益冲突的披露见本文末尾。