Center for Vascular Research, Department of Medicine and Hematology, St George Hospital, St George Clinical School, University of New South Wales, Sydney, 2052, Australia.
Int J Cardiol. 2010 Jan 7;138(1):40-9. doi: 10.1016/j.ijcard.2008.08.032. Epub 2009 Feb 28.
Side population cells are a rare subset of cells found in the adult heart that are highly enriched for stem and progenitor cell activity. Recent studies have suggested that Sca1+/CD31- cardiac side population cells are capable of differentiation into cardiomyocytes in vitro. However, the response of these cells to myocardial injury remains unknown in vivo.
Sca1+/CD31- cardiac side population cells were isolated from mouse (C57BL6/J) hearts by FACS. These cells were labeled and delivered via an intramyocardial injection into an infracted mouse heart. The differentiation potential of these cells was determined by immunohistochemistry two weeks later. We further tested the migration potential and the relationship of SDF-1alpha/CXCR4 to these cells.
The transplanted cells were found to express cardiomyocyte or endothelial cell specific markers. Furthermore, when these cells were transplanted into non-infarct myocardium after myocardial infarction, they were found in the damaged myocardium. Consistent with their homing property, we found that SDF-1alpha and CXCR4 were up-regulated in the damaged myocardium and on Sca1+/CD31- cardiac side population cells respectively following myocardial infarction. We also show that SDF-1alpha induced migration of Sca1+/CD31- cardiac side population cells in vitro.
Our results have suggested that Sca1+/CD31- cardiac side population cells are able to migrate into damaged myocardium from non-ischemic area of the heart and differentiate into both cardiomyocyte- and endothelial-like cells following acute ischemic injury. The SDF-1alpha/CXCR4 system might play an important role in the migration of these cells.
侧群细胞是在成人心脏中发现的一种稀有细胞亚群，其富含干细胞和祖细胞活性。最近的研究表明，Sca1+/CD31-心脏侧群细胞在体外能够分化为心肌细胞。然而，这些细胞对心肌损伤的反应在体内仍然未知。
通过 FACS 从小鼠（C57BL6/J）心脏中分离出 Sca1+/CD31-心脏侧群细胞。这些细胞经过标记后，通过心肌内注射递送到梗死小鼠的心脏中。两周后，通过免疫组织化学法确定这些细胞的分化潜力。我们进一步测试了这些细胞的迁移潜力以及 SDF-1alpha/CXCR4 与之的关系。
移植的细胞被发现表达心肌细胞或内皮细胞特异性标志物。此外，当这些细胞在心肌梗死后被移植到非梗死心肌中时，它们被发现在受损的心肌中。与它们的归巢特性一致，我们发现 SDF-1alpha 和 CXCR4 在心肌梗死后分别在受损的心肌中和 Sca1+/CD31-心脏侧群细胞上上调。我们还表明，SDF-1alpha 诱导 Sca1+/CD31-心脏侧群细胞在体外迁移。
我们的结果表明，Sca1+/CD31-心脏侧群细胞能够从心脏的非缺血区域迁移到受损的心肌中，并在急性缺血损伤后分化为心肌细胞和内皮样细胞。SDF-1alpha/CXCR4 系统可能在这些细胞的迁移中发挥重要作用。
