Nonhematopoletic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction
Nonhematopoletic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction
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DOI：
10.1182/blood-2004-04-1488
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发表时间：
2004-12-01
期刊：
影响因子：
20.3
通讯作者：
Fukuda, K
中科院分区：
文献类型：
--
作者：
Kawada, H;Fujita, J;Fukuda, K
据报道，骨髓（BM）细胞有助于心肌梗死后的再生过程。然而，负责的骨髓细胞尚未完全确定。在这里，我们使用了2个独立的克隆研究来确定骨髓（BM）来源的心肌细胞的来源。首先，我们将来自普遍表达增强绿色荧光蛋白（EGFP）的小鼠的CD34(-) c-kit(+)Sca-1（+）谱系（-）侧群（CD34(-)KSL-SP）细胞或整个BM细胞移植到致死照射的小鼠中，诱导心肌梗死（MI），并用粒细胞集落刺激因子（G-CSF）处理动物以动员干细胞到受损的心肌。在心肌梗死后8周，从100个标本中，我们在接受移植的小鼠的CD34(-) KSL-SP细胞的心肌中只发现了3个EGFP（+）肌动蛋白（+）细胞，但在接受移植的小鼠的整个BM细胞中发现了5000多个EGFP（+）肌动蛋白（+）细胞，这表明大多数EGFP（+）肌动蛋白（+）细胞来源于非造血BM细胞。接下来，将克隆纯化的非造血间充质干细胞（MSCs），即心肌生成细胞（CMG），以心肌细胞特异性的方式表达EGFP，直接移植到致死照射小鼠的BM中，诱导心肌梗死，并用G-CSF处理。缺血心肌中可见EGFP（+）肌动蛋白（+）细胞，表明CMG细胞已被动员并分化为心肌细胞。综上所述，这些结果表明绝大多数bm来源的心肌细胞是MSCs。(C) 2004年由美国血液病学会出版。
Bone marrow (BM) cells are reported to contribute to the process of regeneration following myocardial infarction. However, the responsible BM cells have not been fully identified. Here, we used 2 independent clonal studies to determine the origin of bone marrow (BM)-derived cardiomyocytes. First, we transplanted single CD34(-) c-kit(+)Sca-1(+)lineage(-) side population (CD34(-)KSL-SP) cells or whole BM cells from mice ubiquitously expressing enhanced green fluorescent protein (EGFP) into lethally irradiated mice, induced myocardial infarction (MI), and treated the animals with granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells to the damaged myocardium. At 8 weeks after MI, from 100 specimens we counted only 3 EGFP(+) actinin(+) cells in myocardium of CD34(-) KSL-SP cells in mice that received transplants, but more than 5000 EGFP(+) actinin(+) cells in whole BM cell in mice that received transplants, suggesting that most of EGFP(+) actinin(+) cells were derived from nonhematopoietic BM cells. Next, clonally purified nonhematopoietic mesenchymal stem cells (MSCs), cardiomyogenic (CMG) cells, that expressed EGFP in the cardiomyocyte-specific manner were transplanted directly into BM of lethally irradiated mice, MI was induced, and they were treated with G-CSF. EGFP(+) actinin(+) cells were observed in the ischemic myocardium, indicating that CMG cells had been mobilized and differentiated into cardiomyocytes. Together, these results suggest that the origin of the vast majority of BM-derived cardiomyocytes is MSCs. (C) 2004 by The American Society of Hematology.