Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium
Haematopoietic stem cells adopt mature haematopoietic fates in ischaemic myocardium
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DOI：
10.1038/nature02460
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发表时间：
2004-04-08
期刊：
影响因子：
64.8
通讯作者：
Robbins, RC
中科院分区：
文献类型：
--
作者：
Balsam, LB;Wagers, AJ;Robbins, RC
在组织损伤的条件下，心肌复制和再生已被报道(1)。越来越多的研究者认为成人骨髓（BM）参与了这一过程，表明骨髓是心脏前体细胞的储存库（2-6）。目前尚不清楚哪些骨髓细胞可以促进心肌形成，以及它们是通过转分化还是细胞融合来实现的。在这里，我们研究了c-kit富集的BM细胞、Lin(-) c-kit(+) BM细胞和c-kit(+) Thy1.1(lo) Lin(-) Sca-1（+）长期重建造血干细胞在梗死模型中再生心肌的能力。从表达绿色荧光蛋白（GFP）的转基因小鼠中分离细胞，直接注射到野生型小鼠缺血心肌中。10天后心肌中检测到大量的GFP（+）细胞，但到30天，心肌中检测到的细胞很少。这些GFP（+）细胞不表达心脏组织特异性标志物，但大多数表达造血标志物CD45和骨髓标志物Gr-1。我们还利用GFP(+)-GFP（-）异种小鼠研究了循环细胞在缺血心肌修复中的作用。同样，我们没有发现来自血液的伴侣来源细胞的心肌再生的证据。我们的数据表明，即使在损伤心脏的微环境中，富含c-kit的BM细胞、Lin(-) c-kit(+) BM细胞和c-kit(+) Thy1.1(lo) Lin(-) Sca-1（+）长期重构造血干细胞也只采用传统的造血方式。
Under conditions of tissue injury, myocardial replication and regeneration have been reported(1). A growing number of investigators have implicated adult bone marrow (BM) in this process, suggesting that marrow serves as a reservoir for cardiac precursor cells(2-6). It remains unclear which BM cell(s) can contribute to myocardium, and whether they do so by transdifferentiation or cell fusion. Here, we studied the ability of c-kit-enriched BM cells, Lin(-) c-kit(+) BM cells and c-kit(+) Thy1.1(lo) Lin(-) Sca-1(+) long-term reconstituting haematopoietic stem cells to regenerate myocardium in an infarct model. Cells were isolated from transgenic mice expressing green fluorescent protein (GFP) and injected directly into ischaemic myocardium of wild-type mice. Abundant GFP(+) cells were detected in the myocardium after 10 days, but by 30 days, few cells were detectable. These GFP(+) cells did not express cardiac tissue-specific markers, but rather, most of them expressed the haematopoietic marker CD45 and myeloid marker Gr-1. We also studied the role of circulating cells in the repair of ischaemic myocardium using GFP(+)-GFP(-) parabiotic mice. Again, we found no evidence of myocardial regeneration from blood-borne partner-derived cells. Our data suggest that even in the microenvironment of the injured heart, c-kit-enriched BM cells, Lin(-) c-kit(+) BM cells and c-kit(+) Thy1.1(lo) Lin(-) Sca-1(+) long-term reconstituting haematopoietic stem cells adopt only traditional haematopoietic fates.