Transcoronary delivery of bone marrow cells to the infarcted murine myocardium - Feasibility, cellular kinetics, and improvement in cardiac function
Transcoronary delivery of bone marrow cells to the infarcted murine myocardium - Feasibility, cellular kinetics, and improvement in cardiac function
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DOI：
10.1007/s00395-006-0590-7
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发表时间：
2006-07-01
影响因子：
9.5
通讯作者：
Limbourg, FP
中科院分区：
文献类型：
--
作者：
Templin, C;Kotlarz, D;Limbourg, FP
为了阐明骨髓来源干细胞(BMC)移植治疗心肌梗死(MI)后的细胞动力学和治疗效果，需要有效的标记和传递策略。用细胞示踪剂四甲基罗丹明(TAMRA)体外标记的LIN(-)系阴性骨髓细胞，在荧光显微镜下被可靠地检测，其特异性高于逆转录病毒增强型绿色荧光蛋白(EGFP)标记和检测。静脉注射后，只有极少数细胞进入缺血心肌。应用，但这一数字增加了18倍以上后经冠状动脉交付。12h以上的时间进程和动力学分析表明，心肌定植似乎是一个具有不同消除半衰期的一级衰减的双相过程。大多数细胞在前2小时内迅速消失(t(1/2)40min)，但剩余细胞在缺血心脏中保留的时间明显延长(t(1/2)5.2 h)。相反，骨髓基质细胞在脾中的定植以线性方式增加。心肌梗死后4周，经冠脉输注BMC虽不改变心肌梗死面积，但可增加梗死区毛细血管密度，改善左心功能。结论：经冠脉注射BMC可增加心肌梗死后心肌梗死后的毛细血管密度，改善左心功能，但归巢至缺血区只是短暂的。
Efficient strategies for labelling and delivery of bone marrow derived stem cells (BMCs) are required to elucidate the cellular kinetics and therapeutic effects after BMC transfer for myocardial infarction (MI). Lineage negative (lin(-)) BMCs, labelled ex vivo in a simple procedure with the cell tracker dye tetramethyl-rhodamine (TAMRA), were reliably detected by fluorescence microscopy with higher specificity than retroviral enhanced green fluorescence protein (EGFP) marking and detection. Only few cells entered the ischemic myocardium after intravenous (i.v.) application, but this number increased more than 18-fold after transcoronary delivery. Time course and kinetic analysis over 12 h revealed that myocardial colonization seems to be a biphasic process of first order decay with different elimination half-lives. Most cells are eliminated rapidly during the first 2 h (t(1/2) 40 min), but the remaining cells are retained significantly longer in the ischemic heart (t(1/2) 5.2 h). In contrast, BMC colonization of the spleen increased rather in a linear fashion. Although transcoronary BMC transfusion did not alter infarct size, it increased capillary density in the infarct border zone and improved LV function 4 weeks after MI.In conclusion, BMCs delivered by transcoronary injection increase capillary density and improve LV function after MI although homing to the ischemic heart is only transient.