Cardiomyocyte regeneration from circulating bone marrow cells in mice
Cardiomyocyte regeneration from circulating bone marrow cells in mice
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DOI：
10.1203/01.pdr.0000078275.14079.77
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发表时间：
2003-09-01
影响因子：
3.6
通讯作者：
Ogawa, S
中科院分区：
文献类型：
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作者：
Kuramochi, Y;Fukazawa, R;Ogawa, S
我们研究了循环骨髓细胞（BMC）在心肌细胞再生中的作用。将从表达增强型绿色荧光蛋白（GFP）的转基因小鼠中分离的BMC移植到致死辐射的C57 BL 6小鼠中。骨髓移植（BMT）后5周，GFP阳性细胞的流式细胞术分析证实了移植骨髓的重建。骨髓移植小鼠随后接受左冠状动脉结扎（心肌梗死）或假手术，并在术后1个月或3个月处死。骨髓移植小鼠在1个月（47.1 +/- 5.9%）和3个月（45.3 +/- 7.8%）时的梗死面积相似，2周和8周的超声心动图显示左心室功能下降。在梗死心脏，GFP阳性细胞表达结蛋白和肌钙蛋白T-C的共聚焦显微镜鉴定。GFP和肌钙蛋白T-C双阳性细胞主要位于梗死周围区域（1个月，365 +/- 45个细胞/50个切片; 3个月：458 +/- 100个细胞/50个切片;与非梗死、梗死和假手术区域相比，p < 0.05）。此外，BMC动员和分化为心肌细胞被发现在心肌梗死后1个月内完成。这些结果表明，心肌梗死后循环BMC在心肌细胞中进行动员和分化。未来的研究需要确定负责这种现象的分子信号机制。
We investigated the role of circulating bone marrow cells (BMC) in cardiomyocyte regeneration. BMC, isolated from transgenic mice expressing enhanced green fluorescent protein (GFP), were transplanted into lethally irradiated C57BL6 mice. Five weeks after bone marrow transplantation (BMT), flow cytometric analysis for GFP-positive cells confirmed reconstitution of transplanted bone marrow. Bone marrow transplant mice subsequently underwent left coronary artery ligation (myocardial infarction) or sham-operation, and were killed at 1 mo or 3 mo after operation. Infarct size was similar in bone marrow transplant mice at 1 mo (47.1 +/- 5.9%) and at 3 mo (45.3 +/- 7.8%), and echocardiography at 2 and 8 wk revealed decreasing left ventricular function. In infarcted heart, GFP-positive cells that expressed desmin and troponin T-C were identified by confocal microscopy. GFP and troponin T-C double-positive cells were predominantly in the peri-infarcted region (1 mo, 365 +/- 45 cells/50 sections; 3 mo: 458 +/- 100 cells/50 sections; p < 0.05 versus noninfarct, infarct, and sham-operated regions). Furthermore, BMC mobilization and differentiation into cardiomyocytes was found to be complete within 1 mo after myocardial infarction. These results demonstrate that circulating BMC undergo mobilization and differentiation in cardiac cells after myocardial infarction. Future studies are required to determine the molecular signaling mechanisms responsible for this phenomenon.