A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction
A quantitative, randomized study evaluating three methods of mesenchymal stem cell delivery following myocardial infarction
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DOI：
10.1093/eurheartj/ehi818
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发表时间：
2006-05-01
影响因子：
39.3
通讯作者：
Wilensky, RL
中科院分区：
文献类型：
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作者：
Freyman, T;Polin, G;Wilensky, RL
间充质干细胞（MSCs）是一种罕见的非造血组织的骨髓来源的干细胞前体，在修复梗死心肌方面显示出潜在的希望。这些和类似的细胞类型正在进行临床试验，但对其传递和随后的生物分布缺乏了解。本研究旨在定量比较猪心肌梗死（MI）模型经静脉（IV）、冠状动脉内（IC）或心内膜（EC）给药后MSC的植入率。方法和结果用猪骨髓培养同种异体雄性间充质干细胞。在培养过程中加入铱纳米颗粒并由MSCs内化。通过长时间球囊阻断左中前降支，在母猪（27- 40kg）中诱发心肌梗死。动物（每组n=6）随机分为三种给药方式。在分娩后14 +/- 3天，通过测定梗死灶内离体铱纳米颗粒浓度来确定细胞植入情况。利用DiI和荧光原位杂交（FISH）标记技术确认细胞植入。在骨髓间充质干细胞输注期间，未发现不良事件。然而，在注射IC后，一半的猪表现出远端血流减少。在第14天，梗死区内的平均移植细胞数量显著增加(P
Aims Mesenchymal stem cells (MSCs), rare bone marrow-derived stem cell precursors of non-haematopoietic tissues, have shown promise in potentially repairing infarcted myocardium. These and similar cell types are being tested clinically, but understanding of delivery and subsequent biodistribution is lacking. This study was designed to quantitatively compare MSC engraftment rates after intravenous (IV), intracoronary (IC), or endocardial (EC) delivery in a porcine myocardial infarction (MI) model.Methods and results Allogeneic, male MSCs were cultured from porcine bone marrow aspirates. Iridium nanoparticles were added during culturing and internalized by the MSCs. An MI was induced in female swine (27-40 kg in size) by prolonged balloon occlusion of the mid-left anterior descending artery. Animals (n=6 per group) were randomized to one of three delivery methods. Cellular engraftment was determined 14 +/- 3 days post-delivery by measuring ex-vivo the iridium nanoparticle concentration in the infarct. Confirmation of cellular engraftment utilized both DiI and fluorescence in situ hybridization (FISH) labelling techniques. During MSC infusion, no adverse events were noted. However, following IC infusion, half of the pigs exhibited decreased blood flow distal to the infusion site. At 14 days, the mean number of engrafted cells within the infarct zone was significantly greater (P