Suuronen Erik J, Price Joel, Veinot John P, Ascah Kathryn, Kapila Varun, Guo Xue-Wei, Wong Serena, Mesana Thierry G, Ruel Marc
Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
J Thorac Cardiovasc Surg. 2007 Nov;134(5):1249-58. doi: 10.1016/j.jtcvs.2007.07.028.
OBJECTIVE: Recent evidence suggests that the effects of mesenchymal progenitor cell transplantation into the infarcted myocardium might be mediated by local paracrine angiogenesis. We compared the effects of mesenchymal progenitor cell transplantation versus those of a primarily angiogenic cell, the endothelial progenitor cell, in a rat model of myocardial infarction. METHODS: Twenty-one days after left anterior descending artery ligation, rats were injected in their infarcted anterior myocardium with 1 x 10(6) mesenchymal progenitor cells, 1 x 10(6) endothelial progenitor cells, 5 x 10(5) mesenchymal progenitor cells plus 5 x 10(5) endothelial progenitor cells, or phosphate-buffered saline (n = 6-8 per group). Echocardiography was performed before injection and 4 weeks later, after which rats were killed and immunohistochemical analyses performed. RESULTS: Connexin43 density was greater in cell-treated groups compared with that seen in the phosphate-buffered saline group (by 91.6% +/- 15.2%, P < .001), with no observed difference between cell-treated groups (P > or = .3). Endothelial progenitor cell treatment increased arteriolar density within the infarct border zone (by 297%, 205%, and 101% vs phosphate-buffered saline, mesenchymal progenitor cell, and mesenchymal progenitor cell/endothelial progenitor cell treatment, respectively; P < .01). Postoperative left ventricular ejection fraction (endothelial progenitor cell: 68.3% +/- 9.8% vs mesenchymal progenitor cell/endothelial progenitor cell: 55.0% +/- 11.1%, mesenchymal progenitor cell: 53.0% +/- 6.0%, and phosphate-buffered saline: 49.6% +/- 9.5%) and fractional shortening (endothelial progenitor cell: 32.4% +/- 5.1% vs mesenchymal progenitor cell: 22.5% +/- 5.4% and phosphate-buffered saline: 21.3% +/- 5.3%) were greater in endothelial progenitor cell-treated rats versus those receiving other treatments (all P < .05). Only endothelial progenitor cells prevented further contractile deterioration compared with baseline values (P = .8), whereas other groups had continued loss of function after treatment. CONCLUSION: Compared with the use of mesenchymal progenitor cells, cell transplantation with endothelial progenitor cells after myocardial infarction resulted in better neovascularization and contractility. This suggests that angiogenesis is an important mechanism in attenuating the progression of left ventricular dysfunction after myocardial infarction.
目的：近期证据表明，间充质祖细胞移植至梗死心肌的效应可能由局部旁分泌血管生成介导。我们在大鼠心肌梗死模型中比较了间充质祖细胞移植与主要具有血管生成作用的细胞即内皮祖细胞移植的效果。 方法：在左前降支结扎21天后，向大鼠梗死的前壁心肌注射1×10⁶个间充质祖细胞、1×10⁶个内皮祖细胞、5×10⁵个间充质祖细胞加5×10⁵个内皮祖细胞或磷酸盐缓冲盐水（每组n = 6 - 8）。在注射前及4周后进行超声心动图检查，之后处死大鼠并进行免疫组织化学分析。 结果：与磷酸盐缓冲盐水组相比，细胞治疗组的连接蛋白43密度更高（增加91.6%±15.2%，P <.001），细胞治疗组之间未观察到差异（P≥.3）。内皮祖细胞治疗增加了梗死边缘区内的小动脉密度（与磷酸盐缓冲盐水组、间充质祖细胞组和间充质祖细胞/内皮祖细胞治疗组相比，分别增加297%、205%和101%；P <.01）。术后左心室射血分数（内皮祖细胞组：68.3%±9.8%，间充质祖细胞/内皮祖细胞组：55.0%±11.1%，间充质祖细胞组：53.0%±6.0%，磷酸盐缓冲盐水组：49.6%±9.5%）和缩短分数（内皮祖细胞组：32.4%±5.1%，间充质祖细胞组：22.5%±5.4%，磷酸盐缓冲盐水组：21.3%±5.3%）在内皮祖细胞治疗的大鼠中高于接受其他治疗的大鼠（均P <.05）。与基线值相比，只有内皮祖细胞阻止了收缩功能的进一步恶化（P =.8），而其他组在治疗后功能持续丧失。 结论：与使用间充质祖细胞相比，心肌梗死后内皮祖细胞移植导致更好的新生血管形成和收缩功能。这表明血管生成是减轻心肌梗死后左心室功能障碍进展的重要机制。
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