Hematopoietic stem cells do not repair the infarcted mouse heart
Hematopoietic stem cells do not repair the infarcted mouse heart
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DOI：
10.1016/j.cardiores.2004.11.009
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发表时间：
2005-01-01
影响因子：
10.8
通讯作者：
Zimmer, HG
中科院分区：
文献类型：
--
作者：
Deten, A;Volz, HC;Zimmer, HG
目的：最近的报道表明，造血干细胞(HSC)可以转分化为心肌细胞，并有助于损伤后的心肌再生。这一概念最近受到了一些研究的挑战，这些研究表明，骨髓来源的细胞在直接注入缺血心肌后并未获得心脏表型。方法：在本研究中，我们分析了在慢性心肌梗死(MI)诱导6周后，通过干细胞因子(SCF；200µg/kg/d，7天)和粒细胞集落刺激因子(G-CSF，50µg/kg/d，7天)刺激增加循环中的成人BM细胞对小鼠心脏形态和血流动力学参数的影响。所有动物均在心肌梗死诱导前2周行脾切除，以防止骨髓细胞的隔离。细胞因子治疗在心肌梗死前3天或心肌梗死后6小时开始。结果：在基础静息状态和去甲肾上腺素(NE；1，5，10，25，50和100 ng静注)刺激后，任何治疗组的左、右室(LV和RV)功能与未治疗的MI动物相比均无改善。每例10例)，在MI后6周用超小型1.4F尖端压力传感器插管测量。此外，在组织学或基因表达分析中没有发现心肌再生的迹象。注射骨髓细胞对心脏再生没有明显影响。(C)2004年欧洲心脏病学会。爱思唯尔出版，版权所有。
Objective: Recent reports suggest that hematopoietic stem cells (HSC) can transdifferentiate into cardiomyoctes and contribute to myocardial regeneration after injury. This concept has recently been challenged by studies in which bone-marrow (BM)-derived cells do not acquire a cardiac phenotype after direct injection into ischemic myocardium.Methods: In this study, we analyzed the effect of increased circulating adult BM cells by stimulation with stem cell factor (SCF; 200 mug/kg/d for 7 days) and granulocyte-colony stimulating factor (G-CSF, 50 mug/kg/d for 7 days) or by peripheral delivery of isolated adult BM cells on morphological and hemodynamic parameters of mouse hearts 6 weeks after induction of chronic myocardial infarction (MI). All animals were splenectomized to prevent sequestration of BM cells 2 weeks prior to the induction of MI. Cytokine treatment was initiated either 3 days prior to or 6 h after MI. Isolated, either whole or by magnetic beads lineage-depleted BM cells were injected via a tail vein 6 It after MI.Results: Left and right ventricular (LV and RV) function revealed no improvement in any treatment group when compared to untreated MI animals at baseline resting conditions as well as after stimulation with norepinephrine (NE; 1, 5, 10, 25, 50, and 100 ng bolus i.v. in 10 mul each) as measured by catherization with ultraminiature 1.4 F tip pressure transducers 6 weeks after MI. Moreover, there was no sign of myocardial regeneration in histological or gene expression analyses.Conclusion: Mobilization or i.v. injection of BM cells do not have a measurable effect on cardiac regeneration. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.