Bone marrow-derived cells contribute to infarct remodelling
Bone marrow-derived cells contribute to infarct remodelling
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DOI：
10.1016/j.cardiores.2006.06.013
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发表时间：
2006-09-01
影响因子：
10.8
通讯作者：
Elsaesser, Albrecht
中科院分区：
文献类型：
--
作者：
Moellmann, Helge;Nef, Holger M.;Elsaesser, Albrecht
目的：心肌细胞是非增殖和终末分化细胞的范式最近受到了一些研究的挑战，这些研究报告了骨髓来源的细胞（BMC）转分化为心肌细胞的能力。然而，这些结果是有争议的，不能被其他人复制。因此，我们研究的贡献和潜在的转分化成不同的细胞类型的BMC在小鼠心脏重构过程中与实验myocardialinfarction.Methods：小鼠（C57 BL/6 J）进行亚致死剂量照射，和BM从增强型绿色荧光蛋白（eGFP）转基因小鼠移植。3个月后行冠状动脉结扎术。分别于梗死后7天（n = 13）和21天（n = 12）对心脏进行研究。使用抗肌联蛋白、连接蛋白43、波形蛋白、SMemb α-平滑肌肌动蛋白、CD 45、CD 34、F4/80、BS-1、CD 31和eGFP的抗体进行免疫组织化学染色。结果：经流式细胞仪分析证实骨髓移植成功。冠状动脉闭塞导致41 +/- 6%的左心室梗死。CD 45 +/eGFP+炎性细胞在7天后频繁发现，在21天后程度较低。在25例心脏中，仅3例心肌细胞呈eGFP阳性，但在梗死区有大量的骨髓基质细胞来源的成纤维细胞和肌成纤维细胞。BMC有助于瘢痕组织新生血管生成，但不血管生成在梗死周围和远程zones.Conclusion：转分化的BMC成存活的心肌细胞是一个可以忽略的事件，在正常的修复过程中，心肌损伤后。心肌细胞源性成纤维细胞和肌成纤维细胞以及新生血管生成对梗死后瘢痕形成有重要作用，并可能在瘢痕组织重塑中起重要作用。(c)2006年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: The paradigm that cardiac myocytes are non-proliferating and terminally differentiated cells has recently been challenged by several studies reporting the ability of bone marrow-derived cells (BMC) to transdifferentiate into cardiomyocytes. However, these results are controversial and could not be reproduced by others. Therefore, we studied the contribution and potential transdifferentiation of BMC into different cell types during the remodelling process in mouse hearts with experimental myocardial infarction.Methods: Mice (C57BL/6J) were sublethally irradiated, and BM from enhanced green fluorescent protein (eGFP)-transgenic mice was transplanted. Coronary artery ligation was performed 3 months later. The hearts were studied 7 days (n = 13) and 21 days (n = 12) after infarction. Immunohistochemical staining was performed using antibodies against titin, connexin 43, vimentin, SMemb alpha-smooth muscle actin, CD45, CD34, F4/80, BS-1, CD31, and eGFP. Sections were analyzed using fluorescence and confocal laser microscopy.Results: Success of BM transplantation was confirmed by FACS analysis. Occlusion of the coronary artery resulted in infarct sizes of 41 +/- 6% of the left ventricle. CD45+/eGFP+ inflammatory cells were found frequently after 7 days and to a lesser degree after 21 days. In 25 examined hearts, only 3 eGFP-positive cardiomyocytes were found. However, numerous BMC-derived fibroblasts and myofibroblasts were found in the infarct area. BMC contributed to scar tissue neoangiogenesis but not to angiogenesis in the periinfarct and remote zones.Conclusion: Transdifferentiation of BMC into viable cardiomyocytes is a negligible event in normal repair processes after myocardial damage. MC-derived fibroblasts and myofibroblasts as well as neoangiogenesis significantly contribute to post-infarction scar fort-nation and might be important in scar tissue remodelling. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.