University of Minnesota Health Science Center, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
Am J Physiol Heart Circ Physiol. 2010 May;298(5):H1348-56. doi: 10.1152/ajpheart.01100.2009. Epub 2010 Feb 19.
The study examined the long-term outcome of cardiac stem cell transplantation in hearts with postinfarction left ventricular (LV) remodeling. Myocardial infarction (MI) was created by ligating the first and second diagonal branches of the left anterior descending coronary artery in miniature swine. Intramyocardial injections of 50 million LacZ-labeled bone marrow-derived multipotent progenitor cells (MPC) were performed in the periscar region (Cell, n = 7) immediately after MI, whereas, in control animals (Cont, n = 7), saline was injected. Functional outcome was assessed monthly for 4 mo with MRI and (31)P-magnetic resonance spectroscopy. Engraftment was studied on histology, and gene chip (Affymetrix) array analysis was used to study differential expression of genes in the two groups. MPC treatment resulted in improvement of ejection fraction as early as 10 days after MI (Cell, 43.4 +/- 5.1% vs. Cont, 32.2 +/- 5.5%; P < 0.05). This improvement was seen each month and persisted to 4 mo (Cell, 51.2 +/- 4.8% vs. Cont, 35.7 +/- 5.0%; P < 0.05). PCr-to-ATP ratio (PCr/ATP) improved with MPC transplantation, which was most pronounced at high cardiac work states (subendocardial PCr/ATP was 1.70 +/- 0.10 vs. 1.34 +/- 0.14, P < 0.05). There was no significant difference in scar size (scar/LV area * 100) at 10 days postinfarction. However, at 4 mo, there was a significant decrease in scar size in the Cell group (Cell, 4.6 +/- 1.0% vs. Cont, 8.6 +/- 2.4%; P < 0.05). No significant engraftment of MPC was observed. MPC transplantation was associated with a downregulation of mitochondrial oxidative enzymes and increased levels of myocyte enhancer factor 2a and zinc finger protein 91. In conclusion, MPC transplantation leads to long-term functional and bioenergetic improvement in a porcine model of postinfarction LV remodeling, despite no significant engraftment of stem cells in the heart. MPC transplantation reduces regional wall stresses and infarct size and mitigates the adverse effects of LV remodeling, as seen by a reduction in LV hypertrophy and LV dilatation, and is associated with differential expression of genes relating to metabolism and apoptosis.
该研究探讨了心脏梗死后左心室（LV）重构患者心脏干细胞移植的长期预后。通过结扎小型猪前降支的第一和第二对角支来制造心肌梗死（MI）。在 MI 后立即在心脏peri 区注射 5000 万个 LacZ 标记的骨髓多能祖细胞（MPC）（细胞，n = 7），而在对照动物（对照，n = 7）中，注射生理盐水。在 4 个月内每月通过 MRI 和（31）P 磁共振波谱评估功能结果。在组织学上研究了植入情况，并使用基因芯片（Affymetrix）阵列分析来研究两组之间基因的差异表达。MPC 治疗可使 MI 后 10 天的射血分数尽早改善（细胞，43.4 +/- 5.1% vs. 对照，32.2 +/- 5.5%；P <0.05）。这种改善每个月都有，持续到 4 个月（细胞，51.2 +/- 4.8% vs. 对照，35.7 +/- 5.0%；P <0.05）。PCr-ATP 比（PCr/ATP）随着 MPC 移植而改善，在高心脏工作状态下最为明显（心内膜下 PCr/ATP 为 1.70 +/- 0.10 比 1.34 +/- 0.14，P <0.05）。梗死后 10 天，疤痕大小（疤痕/LV 面积 * 100）无明显差异。然而，在 4 个月时，细胞组的疤痕大小明显减少（细胞，4.6 +/- 1.0% vs. 对照，8.6 +/- 2.4%；P <0.05）。未观察到 MPC 的明显植入。MPC 移植与线粒体氧化酶的下调以及肌细胞增强因子 2a 和锌指蛋白 91 的水平升高有关。总之，在猪梗死后 LV 重构模型中，MPC 移植可导致长期的功能和生物能量改善，尽管心脏中干细胞的植入没有明显增加。MPC 移植可降低局部壁应力和梗死面积，并减轻 LV 重构的不良影响，表现为 LV 肥厚和 LV 扩张减少，并与与代谢和凋亡相关的基因的差异表达有关。
