Schuh Alexander, Konschalla Simone, Kroh Andreas, Schober Andreas, Marx Nikolaus, Sonmez Tolga Taha, Zenke Martin, Sasse Alexander, Liehn Elisa A
Institute for Molecular Cardiovascular Research (IMCAR), Universitätsklinikum der RWTH Aachen, Pauwelsstrasse 30, 52057 Aachen, Germany.
Curr Pharm Des. 2014;20(12):1964-70. doi: 10.2174/13816128113199990443.
Aim of the presented study was to investigate the role of stromal derived factor 1 (SDF-1α) in mobilizing stem cells in combination with endothelial progenitor cell (EPC) transplantation in a regenerative strategy for myocardial infarction therapy in a murine ischemia/reperfusion model. Initially bone marrow was eradicated and reconstituted with the use of green fluorescent protein (GFP) labelled allogenic cells. After reconstitution, myocardial ischemia was induced by temporary ligation of the left anterior descending coronary artery (LAD) in C57/B16 mice and maintained for 1h. After reperfusion, EPCs (1 x 10(6) cells) or medium were injected directly into the border zones of the infarcted areas. In addition, the animals were divided in groups treated or not with specific antibodies against SDF-1α. 4 weeks after transplantation, echocardiography revealed a significantly decreased left ventricular function after application of EPCs in anti-SDF-1α treated animals compared to untreated groups. Histology revealed that EPC transplantation and anti-SDF-1α treatment diminished the amount of intramyocardially attracted GFP positive bone marrow cells. Interestingly, no significant changes in the density of CD31+ vessel structures compared to EPC transplantation alone were detectable in anti-SDF-1α treated groups. Anti-SDF-1α treatment also increased numbers of inflammatory cells (monocytes and neutrophiles) in infarcted areas. Rate of apoptotic cells and proliferation after transplantation did not differ. In conclusion, transplanted endothelial progenitor cells as well as SDF-1α are key factors in mobilization of endogenous bone marrow cells towards infarcted myocardium. Anti-SDF-1α treatment leads to a significant decreased left ventricular function, alters the inflammatory processes, but does not lead to significant alterations in neovascularization or collagen content of infarcted areas.
本研究的目的是在小鼠缺血/再灌注模型的心肌梗死治疗再生策略中，研究基质衍生因子1（SDF-1α）在与内皮祖细胞（EPC）移植联合动员干细胞中的作用。最初，使用绿色荧光蛋白（GFP）标记的同种异体细胞根除并重建骨髓。重建后，通过暂时结扎C57/B16小鼠的左冠状动脉前降支（LAD）诱导心肌缺血，并维持1小时。再灌注后，将EPCs（1×10⁶个细胞）或培养基直接注射到梗死区域的边缘区。此外，将动物分为用抗SDF-1α特异性抗体治疗或未治疗的组。移植后4周，超声心动图显示，与未治疗组相比，抗SDF-1α治疗的动物应用EPCs后左心室功能显著降低。组织学显示，EPC移植和抗SDF-1α治疗减少了心肌内吸引的GFP阳性骨髓细胞数量。有趣的是，在抗SDF-1α治疗组中，与单独EPC移植相比，CD31⁺血管结构密度没有显著变化。抗SDF-1α治疗还增加了梗死区域炎症细胞（单核细胞和中性粒细胞）的数量。移植后凋亡细胞率和增殖率没有差异。总之，移植的内皮祖细胞以及SDF-1α是内源性骨髓细胞向梗死心肌动员的关键因素。抗SDF-1α治疗导致左心室功能显著降低，改变炎症过程，但不会导致梗死区域新生血管形成或胶原含量的显著改变。
