Santo Stefano Di, Tepper Oren M, von Ballmoos Moritz Wyler, Diehm Nicolas, Völzmann Jan, Baumgartner Iris, Kalka Christoph
Division of Vascular Medicine, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, Freiburgstrasse, CH-3010 Bern, Switzerland.
Thromb Haemost. 2009 Mar;101(3):460-4.
Endothelial progenitor cells (EPC) are involved in many healing processes in cardiovascular diseases and can be found in spontaneously resolving venous thrombi. The purpose of the present study was to investigate whether the therapeutic administration of EPC might enhance the resolution of venous thrombi. For this purpose, venous thrombosis was induced in the infrarenal inferior vena cava (IVC) in 28 athymic nude rats. Culture expanded EPC derived from human peripheral blood mononuclear cells were injected intravenously two and four days after thrombus induction. Recanalisation of the IVC and thrombus organisation were assessed by laser Doppler measurements of the blood flow and immunohistochemical detection of endothelialised luminal structures in the thrombus. EPC transplantation resulted in significantly enhanced thrombus neovascularisation (capillary density: 186.6 +/- 26.7/HPF vs. 78 +/- 12.3/HPF, p<0.01; area covered by capillaries: 8.9 +/- 1.7 microm(2) vs. 2.5 +/- 1.3 microm(2), p<0.01) and was accompanied by a substantial increase in intra-thrombus blood flow (perfusion ratio: 0.7 +/- 0.07 vs. 0.3 +/- 0.08, p<0.02). These results were paralleled by augmented macrophage recruitment into resolving thrombi in the animals treated with EPC (39.4 +/- 4.7/HPF vs. 11.6 +/- 1.9/HPF, p<0.01). Our data suggest that EPC transplantation might be of clinical value to facilitate venous thrombus resolution in cases where current therapeutic options have limited success.
内皮祖细胞（EPC）参与心血管疾病的多种愈合过程，且可在自然溶解的静脉血栓中发现。本研究的目的是调查EPC的治疗性给药是否可能增强静脉血栓的溶解。为此，在28只无胸腺裸鼠的肾下下腔静脉（IVC）中诱导静脉血栓形成。在血栓形成后第2天和第4天，静脉注射源自人外周血单个核细胞的培养扩增EPC。通过激光多普勒测量血流以及免疫组织化学检测血栓中内皮化的管腔结构，评估IVC的再通和血栓机化。EPC移植导致血栓新生血管形成显著增强（毛细血管密度：186.6±26.7/HPF对78±12.3/HPF，p<0.01；毛细血管覆盖面积：8.9±1.7μm²对2.5±1.3μm²，p<0.01），并伴有血栓内血流的大幅增加（灌注率：0.7±0.07对0.3±0.08，p<0.02）。在用EPC治疗的动物中，这些结果与溶解血栓中巨噬细胞募集增加相平行（39.4±4.7/HPF对11.6±1.9/HPF，p<0.01）。我们的数据表明，在当前治疗选择效果有限的情况下，EPC移植可能对促进静脉血栓溶解具有临床价值。
