Ankersmit H J, Hoetzenecker K, Dietl W, Soleiman A, Horvat R, Wolfsberger M, Gerner C, Hacker S, Mildner M, Moser B, Lichtenauer M, Podesser B K
Department of Surgery, Medical University of Vienna, Vienna, Austria.
Eur J Clin Invest. 2009 Jun;39(6):445-56. doi: 10.1111/j.1365-2362.2009.02111.x. Epub 2009 Apr 16.
Acute myocardial infarction (AMI) is followed by post AMI cardiac remodelling, often leading to congestive heart failure. Homing of c-kit+ endothelial progenitor cells (EPC) has been thought to be the optimal source for regenerating infarcted myocardium.
Immune function of viable peripheral blood mononuclear cells (PBMC) was evaluated after co-culture with irradiated apoptotic PBMC (IA-PBMC) in vitro. Viable PBMC, IA-PBMC and culture supernatants (SN) thereof were obtained after 24 h. Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were utilized to quantify interleukin-8 (IL-8), vascular endothelial growth factor, matrix metalloproteinase-9 (MMP9) in PBMC, SN and SN exposed fibroblasts. Cell suspensions of viable- and IA-PBMC were infused in an experimental rat AMI model. Immunohistological analysis was performed to detect inflammatory and pro-angiogenic cells within 72 h post-infarction. Functional data and determination of infarction size were quantified by echocardiography and Elastica van Gieson staining.
The IA-PBMC attenuated immune reactivity and resulted in secretion of pro-angiogenic IL-8 and MMP9 in vitro. Fibroblasts exposed to viable and IA-PBMC derived SN caused RNA increment of IL-8 and MMP9. AMI rats that were infused with IA-PBMC cell suspension evidenced enhanced homing of endothelial progenitor cells within 72 h as compared to control (medium alone, viable-PBMC). Echocardiography showed a significant reduction in infarction size and improvement in post AMI remodelling as evidenced by an attenuated loss of ejection fraction.
These data indicate that infusion of IA-PBMC cell suspension in experimental AMI circumvented inflammation, caused preferential homing of regenerative EPC and replaced infarcted myocardium.
急性心肌梗死（AMI）后会发生心肌梗死后心脏重构，常导致充血性心力衰竭。c-kit+内皮祖细胞（EPC）归巢被认为是梗死心肌再生的最佳来源。
体外将活的外周血单个核细胞（PBMC）与经辐照的凋亡PBMC（IA-PBMC）共培养后，评估活的PBMC的免疫功能。24小时后获得活的PBMC、IA-PBMC及其培养上清液（SN）。利用逆转录聚合酶链反应和酶联免疫吸附测定法对PBMC、SN和暴露于SN的成纤维细胞中的白细胞介素-8（IL-8）、血管内皮生长因子、基质金属蛋白酶-9（MMP9）进行定量。将活的和IA-PBMC的细胞悬液注入实验性大鼠AMI模型。进行免疫组织学分析以检测梗死后72小时内的炎症细胞和促血管生成细胞。通过超声心动图和弹性纤维染色对功能数据和梗死面积测定进行定量。
IA-PBMC在体外减弱了免疫反应性，并导致促血管生成的IL-8和MMP9分泌。暴露于活的和IA-PBMC来源的SN的成纤维细胞导致IL-8和MMP9的RNA增加。与对照组（仅培养基、活的PBMC）相比，注入IA-PBMC细胞悬液的AMI大鼠在72小时内显示内皮祖细胞归巢增强。超声心动图显示梗死面积显著减小，心肌梗死后重构得到改善，射血分数损失减弱证明了这一点。
这些数据表明，在实验性AMI中注入IA-PBMC细胞悬液可规避炎症，导致再生EPC优先归巢并替代梗死心肌。
