Misao Yu, Takemura Genzou, Arai Masazumi, Sato Shigeru, Suzuki Koji, Miyata Shusaku, Kosai Ken-ichiro, Minatoguchi Shinya, Fujiwara Takako, Fujiwara Hisayoshi
Department of Cardiology, Regeneration Medicine and Bioethics, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Cardiovasc Res. 2006 Feb 1;69(2):476-90. doi: 10.1016/j.cardiores.2005.11.001. Epub 2005 Dec 20.
Whether bone marrow cells injected following acute myocardial infarction (MI) transdifferentiate into cardiomyocytes remains controversial, and how these cells affect repair-related cytokines is not known.
Autologous bone marrow-derived mononuclear cells (BM-MNCs) labeled with DiI, 1,1'-dioctadecyl-1 to 3,3,3',3'-tetramethylindocarbocyanine perchlorate, or saline were intravenously injected into rabbits 5 h following a 30-min ischemia and reperfusion protocol, and cardiac function and the general pathology of the infarcted heart were followed up 1 and 3 months post-MI. To search for regenerated myocardium, electron microscopy as well as confocal microscopy were performed in the infarcted myocardium 7 days post-MI. Expression levels of repair-related cytokines were evaluated by immunohistochemistry and Western blotting.
Improvements in cardiac function and reductions in infarct size were observed in the BM-MNC group 1 month and 3 months post-MI. Using electron microscopy 7 days after infarction, clusters of very immature (fetal) and relatively mature cardiomyocytes undergoing differentiation were identified in the infarcted anterior LV wall in the BM-MNC group, though their numbers were small. These cells contained many small and dense DiI particles (a BM-MNC marker), indicating that cardiomyocytes had regenerated from the injected BM-MNCs. The expression of both transforming growth factor-beta, which stimulates collagen synthesis and matrix metalloproteinase-1, a collagenase, were both down-regulated 7 days and 1 month post-MI in the BM-MNC group. Stromal cell-derived factor-1, which is known to recruit BM-MNCs into target tissues, was overexpressed in the infarcted areas of BM-MNC hearts 7 days post-MI.
Intravenous transplantation of BM-MNCs leads to the development of BM-MNC-derived myocyte-like cells and regulates the expression of repair-related cytokines that facilitate repair following myocardial infarction.
急性心肌梗死（MI）后注射的骨髓细胞是否转分化为心肌细胞仍存在争议，且这些细胞如何影响与修复相关的细胞因子尚不清楚。
在30分钟缺血再灌注方案后5小时，将用DiI（1,1'-二辛基-1-3,3,3',3'-四甲基吲哚碳菁高氯酸盐）标记的自体骨髓来源的单核细胞（BM-MNCs）、生理盐水静脉注射到兔子体内，在心肌梗死后1个月和3个月对心脏功能和梗死心脏的大体病理进行随访。为了寻找再生心肌，在心肌梗死后7天对梗死心肌进行电子显微镜和共聚焦显微镜检查。通过免疫组织化学和蛋白质印迹法评估与修复相关的细胞因子的表达水平。
在心肌梗死后1个月和3个月，BM-MNC组观察到心脏功能改善和梗死面积减小。梗死7天后使用电子显微镜，在BM-MNC组梗死的左心室前壁中发现了正在分化的非常不成熟（胎儿型）和相对成熟的心肌细胞簇，尽管数量很少。这些细胞含有许多小而密集的DiI颗粒（一种BM-MNC标志物），表明心肌细胞已从注射的BM-MNCs再生。在BM-MNC组中，刺激胶原蛋白合成的转化生长因子-β和胶原蛋白酶基质金属蛋白酶-1的表达在心肌梗死后7天和1个月均下调。已知可将BM-MNCs募集到靶组织中的基质细胞衍生因子-1在心肌梗死后7天在BM-MNC心脏的梗死区域中过度表达。
静脉内移植BM-MNCs导致BM-MNC来源的心肌样细胞的发展，并调节促进心肌梗死后修复的与修复相关的细胞因子的表达。
