Möllmann Helge, Nef Holger M, Kostin Sawa, von Kalle Christof, Pilz Ingo, Weber Michael, Schaper Jutta, Hamm Christian W, Elsässer Albrecht
Kerckhoff Heart Center, Benekestrasse 2-8, 61231 Bad Nauheim, Germany.
Cardiovasc Res. 2006 Sep 1;71(4):661-71. doi: 10.1016/j.cardiores.2006.06.013. Epub 2006 Jun 14.
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.
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.
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.
Transdifferentiation of BMC into viable cardiomyocytes is a negligible event in normal repair processes after myocardial damage. BMC-derived fibroblasts and myofibroblasts as well as neoangiogenesis significantly contribute to post-infarction scar formation and might be important in scar tissue remodelling.
心肌细胞是不增殖的终末分化细胞这一范例最近受到了几项研究的挑战，这些研究报道骨髓来源的细胞（BMC）能够转分化为心肌细胞。然而，这些结果存在争议，其他研究无法重复。因此，我们研究了在实验性心肌梗死的小鼠心脏重塑过程中，BMC对不同细胞类型的贡献及其潜在的转分化情况。
对C57BL/6J小鼠进行亚致死剂量照射，然后移植来自增强型绿色荧光蛋白（eGFP）转基因小鼠的骨髓。3个月后进行冠状动脉结扎。在梗死7天（n = 13）和21天（n = 12）后对心脏进行研究。使用抗肌联蛋白、连接蛋白43、波形蛋白、平滑肌肌动蛋白α、CD45、CD34、F4/80、BS-1、CD31和eGFP的抗体进行免疫组织化学染色。使用荧光和共聚焦激光显微镜对切片进行分析。
通过流式细胞术分析证实了骨髓移植成功。冠状动脉闭塞导致梗死面积占左心室的41±6%。7天后经常发现CD45+/eGFP+炎性细胞，21天后程度较轻。在25个检查的心脏中，仅发现3个eGFP阳性心肌细胞。然而，在梗死区域发现了大量源自BMC的成纤维细胞和肌成纤维细胞。BMC有助于梗死区域瘢痕组织的新生血管形成，但对梗死周边和远处区域的血管生成没有贡献。
在心肌损伤后的正常修复过程中，BMC转分化为有活力的心肌细胞是一个可忽略不计的事件。源自BMC的成纤维细胞和肌成纤维细胞以及新生血管形成对梗死后瘢痕形成有显著贡献，并且可能在瘢痕组织重塑中起重要作用。
