Differentiation and migration of Sca1+/CD31-cardiac side population cells in a murine myocardial ischemic model
Differentiation and migration of Sca1+/CD31-cardiac side population cells in a murine myocardial ischemic model
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DOI：
10.1016/j.ijcard.2008.08.032
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发表时间：
2010-01-07
影响因子：
3.5
通讯作者：
Chong, Beng
中科院分区：
文献类型：
--
作者：
Liang, Simon X.;Tan, Terence Y. L.;Chong, Beng
背景：侧群细胞是在成人心脏中发现的罕见细胞亚群，其干细胞和祖细胞活性高度富集。最近的研究表明，Sca1+/CD31-心脏侧群细胞能够在体外分化为心肌细胞。然而，这些细胞在体内对心肌损伤的反应仍不清楚。方法：通过FACS从小鼠(C57BL6/J)心脏中分离Sca1+/CD31-心脏侧群细胞。这些细胞被标记并通过心肌内注射输送到梗塞的小鼠心脏中。两周后通过免疫组织化学测定这些细胞的分化潜力。我们进一步测试了迁移潜力以及SDF-1α/CXCR4与这些细胞的关系。结果：发现移植的细胞表达心肌细胞或内皮细胞特异性标记物。此外，当这些细胞被移植到心肌梗塞后的非梗塞心肌中时，在受损的心肌中也发现了它们。与它们的归巢特性一致，我们发现心肌梗死后受损心肌和 Sca1+/CD31- 心脏侧细胞群中 SDF-1 α 和 CXCR4 分别上调。我们还表明，SDF-1 α 在体外诱导 Sca1+/CD31- 心脏侧群细胞迁移。结论：我们的结果表明，Sca1+/CD31- 心脏侧群细胞能够从心脏非缺血区域迁移到受损心肌中，并在急性缺血损伤后分化为心肌细胞样细胞和内皮样细胞。 SDF-1 α/CXCR4 系统可能在这些细胞的迁移中发挥重要作用。 (C) 2009 Elsevier Ireland Ltd. 保留所有权利。
Background: 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.Methods: 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-1 alpha/CXCR4 to these cells.Results: 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-1 alpha 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-1 alpha induced migration of Sca1+/CD31- cardiac side population cells in vitro.Conclusions: 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-1 alpha/CXCR4 system might play an important role in the migration of these cells. (C) 2009 Elsevier Ireland Ltd. All rights reserved.