Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia
Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia
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DOI：
10.1016/s0735-1097(01)01200-1
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发表时间：
2001-05-01
影响因子：
24
通讯作者：
Kornowski, R
中科院分区：
文献类型：
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作者：
Fuchs, S;Baffour, R;Kornowski, R
我们检验了心肌内注射自体骨髓（ABM）促进缺血猪心肌侧支循环发育的假设。我们还确定，在体外，是否骨髓（BM）细胞分泌血管内皮生长因子（VEGF）和巨噬细胞趋化蛋白-1（MCP-1）。背景的自然过程导致侧支发展是极其复杂的，需要多种生长因子相互作用的音乐会和序列。由于最佳的血管生成可能因此需要多种血管生成因子，我们认为注射含有分泌多种血管生成因子的细胞的BM可能提供最佳的治疗性血管生成。测定条件培养基中VEGF和MCP-1的含量，并将其加入培养的猪主动脉内皮细胞（PAEC）中以评估增殖。左回旋支Ameroid植入后4周，经心内膜向缺血区注射新鲜抽吸的ABM（n = 7）或肝素化生理盐水（n = 7）（12个部位0.2 ml/注射）。在静息和应激期间进行超声心动图评估心肌增厚，并进行微球评估灌注。结果血管内皮生长因子和MCP-1浓度呈时间相关性增加。条件培养基以剂量相关的方式增强PAEC增殖。侧支血流（缺血/正常区X 100在ABM处理的猪中得到改善（ABM：在休息时98 +/- 14对83 +/- 12，p = 0.001;在腺苷期间89 +/- 18对78 +/- 12，p = 0.025;对照：在休息时92 +/- 10对89 +/- 9，p = 0.49; 78 +/- 11 vs.77 +/- 5，p = 0.75）。同样，ABM处理猪的收缩性增加（ABM：静息时83 +/- 21 vs. 60 +/- 32，p = 0.04;起搏期间91 +/- 44 vs. 36 +/- 43，p = 0.056;对照组：静息时69 +/- 48 vs. 64 +/- 46，p = 0.74;结论：骨髓细胞分泌血管生成因子，诱导内皮细胞增殖，经心内膜注射，增加缺血心肌侧支循环灌注和心肌功能。（J Am Coil Cardiol 2001;37：1726-32）（C）美国心脏病学会2001年。
OBJECTIVES We tested the hypothesis that intramyocardial injection of autologous bone marrow (ABM) promotes collateral development in ischemic porcine myocardium. We also defined, in vitro, whether bone marrow (BM) cells secrete vascular endothelial growth factor (VEGF) and macrophage chemoattractant protein-1 (MCP-1).BACKGROUND The natural processes leading to collateral development are extremely complex, requiring multiple growth factors interacting in concert and in sequence. Because optimal angiogenesis may therefore, require multiple angiogenic factors, we thought that injection of BM, which contains cells that secrete numerous angiogenic factors, might provide optimal therapeutic angiogenesis,METHODS Bone marrow was cultured four weeks in vitro. Conditioned medium was assayed for VEGF and MCP-1 and was added to cultured pig aortic endothelial cells (PAEC) to assess proliferation. Four weeks after left circumflex ameroid implantation, freshly aspirated ABM (n = 7) or heparinized saline (n = 7) was injected transendocardially into the ischemic zone (0.2 ml/injection at 12 sites). Echocardiography to assess myocardial thickening and microspheres to assess perfusion were performed at rest and during stress.RESULTS Vascular endothelial growth factor and MCP-1 concentrations increased in a time-related manner. The conditioned medium enhanced, in a dose related manner, PAEC proliferation. Collateral flow (ischemic/normal zone X 100 improved in ABM-treated pigs (ABM: 98 +/- 14 vs. 83 +/- 12 at rest, p = 0.001; 89 +/- 18 vs. 78 +/- 12 during adenosine, p = 0.025; controls: 92 +/- 10 vs. 89 +/- 9 at rest, p = 0.49; 78 +/- 11 vs.77 +/- 5 during adenosine, p = 0.75). Similarly, contractility increased in ABM-treated pigs (ABM: 83 +/- 21 vs, 60 +/- 32 at rest, p = 0.04; 91 +/- 44 vs. 36 +/- 43 during pacing, p = 0.056; controls: 69 +/- 48 vs. 64 +/- 46 at rest, p = 0.74; 65 +/- 56 vs. 37 +/- 56 during pacing, p = 0.23).CONCLUSIONS Bone marrow cells secrete angiogenic factors that induce endothelial cell proliferation and, when injected transendocardially, augment collateral perfusion and myocardial function in ischemic myocardium. (J Am Coil Cardiol 2001;37:1726-32) (C) 2001 by the American College of Cardiology.