Ex vivo activated human macrophages improve healing, remodeling, and function of the infarcted heart
Ex vivo activated human macrophages improve healing, remodeling, and function of the infarcted heart
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DOI：
10.1161/circulationaha.105.000331
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发表时间：
2006-07-04
期刊：
影响因子：
37.8
通讯作者：
Danon, David
中科院分区：
文献类型：
--
作者：
Leor, Jonathan;Rozen, Liat;Danon, David
背景活化的巨噬细胞在伤口愈合和受损组织修复中具有重要作用。我们试图探索体外活化巨噬细胞促进梗死心肌愈合和修复的能力。方法与结果：以年轻献血者全血为原料，在封闭无菌系统中制备人活化巨噬细胞悬液（AMS），并采用新型低渗透休克方法进行活化。AMS（约为4X10(5)个细胞）包含高达43%的cd14阳性细胞，并在冠状动脉结扎后立即注射到大鼠（n=8）的缺血心肌中。对照组（n=9）给予生理盐水注射。通过组织学、人生长激素特异性聚合酶链反应和氧化铁纳米颗粒标记细胞的磁共振成像（MRI）跟踪显示，注射后4 ~ 7天，人细胞在梗死心脏中存在。5周后，疤痕血管密度（+/- SE） （25 +/- 4 vs 10 +/- 1 / mm）；P < 0.05)，肌成纤维细胞积累、常驻单核细胞和巨噬细胞的募集在ams处理的心脏中比对照组更大。注射前和注射后5周的连续超声心动图研究显示，与对照组相比，AMS改善了疤痕增厚（0.15 +/- 0.01比0.11 +/- 0.01 cm, P < 0.05），降低了左室（LV）舒张扩张（0.87 +/- 0.02比0.99 +/- 0.04 cm, P < 0.05），改善了左室分数缩短（31 +/- 2比20 +/- 4%，P < 0.05）。结论：心肌梗死后早期注射AMS可促进血管形成和组织修复，改善心脏重构和功能。我们的工作提出了一种新的临床相关的选择，以促进缺血组织的修复。
Background-Activated macrophages have a significant role in wound healing and damaged tissue repair. We sought to explore the ability of ex vivo activated macrophages to promote healing and repair of the infarcted myocardium.Methods and Results-Human activated macrophage suspension (AMS) was prepared from a whole blood unit obtained from young donors in a closed sterile system and was activated by a novel method of hypo-osmotic shock. The AMS (approximate to 4X10(5) cells) included up to 43% CD14-positive cells and was injected into the ischemic myocardium of rats (n=8) immediately after coronary artery ligation. The control group (n=9) was treated with saline injection. The human cells existed in the infarcted heart 4 to 7 days after injection, as indicated by histology, human growth hormone-specific polymerase chain reaction, and magnetic resonance imaging (MRI) tracking of iron oxide-nanoparticle-labeled cells. After 5 weeks, scar vessel density (+/- SE) (25 +/- 4 versus 10 +/- 1 per mm(2); P < 0.05), myofibroblast accumulation, and recruitment of resident monocytes and macrophages were greater in AMS-treated hearts compared with controls. Serial echocardiography studies, before and 5 weeks after injection, showed that AMS improved scar thickening (0.15 +/- 0.01 versus 0.11 +/- 0.01 cm; P < 0.05), reduced left ventricular (LV) diastolic dilatation (0.87 +/- 0.02 versus 0.99 +/- 0.04 cm; P < 0.05), and improved LV fractional shortening (31 +/- 2 versus 20 +/- 4%; P < 0.05), compared with controls.Conclusions-Early after myocardial infarction, injection of AMS accelerates vascularization, tissue repair, and improves cardiac remodeling and function. Our work suggests a novel clinically relevant option to promote the repair of ischemic tissue.