Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Acta Biochim Biophys Sin (Shanghai). 2011 Nov;43(11):857-66. doi: 10.1093/abbs/gmr087. Epub 2011 Oct 6.
Mesenchymal stem cells (MSCs) have been extensively applied for the restoration of cardiomyocytes loss after acute myocardial infarction (AMI). However, the optimal therapeutic efficacy of MSCs in ischemic heart diseases has been hampered by their poor survival and low differentiated rates. Therefore, the improvement of MSC survival and differentiated rates is warranted and critical for the efficacy of MSCs in AMI. In this paper, MSCs isolated from rat inguinal fat tissues were termed as adipose-derived mesenchymal stem cells (ASCs), and the fourth passage of ASCs was pre-specified by co-culturing with cardiomyocytes in a transwell system termed as co-ASCs. Fourteen days later, GATA-4 (a transcription factor) and cardiac troponin-I were detected by cellular immunofluorescence. Atorvastatin (Ator group) or vehicle (control group) was administrated for the first 24 h after AMI production in rats. Fourteen days later, inflammatory parameters and cardiac function were evaluated. The other surviving rats were injected with a total of 1 × 10(6) co-ASCs/100 μl phosphate-buffered saline (PBS), 1×10(6) ASCs/100 μl PBS, or 100 μl PBS. Twenty-eight days after cell injection, survival and differentiated rates of transplanted cells and cardiac function were evaluated. The percentage of GATA-4 expression in co-ASCs was 28.5% ± 5.6% and of cardiac troponin-I was 22.8% ± 3.2%. Compared with the control group, the number of infiltrating inflammatory cells, myeloperoxidase activity, inflammatory cytokines (VCAM-1, TNF-α, Hs-CRP) mRNA expression, and Bax protein expression were significantly reduced in the three Ator groups, accompanied by a significant improvement of Bcl-2 protein expression and cardiac function (P< 0.05). Compared with the Ator2 + ASCs group and Con + co-ASCs group, the number of 4-6-diamidino-2-phenylindole-stained cells and cardiac troponin-I-positive transplanted cells, concomitant with cardiac function, were improved most prominently in the Ator3 + co-ASCs group (P< 0.05). Pre-amelioration of the cardiac milieu, in conjunction with pre-specification of ASCs, was beneficial for enhancing ASCs' therapeutic efficacy on cardiac function after AMI.
间充质干细胞（MSCs）已被广泛应用于修复急性心肌梗死（AMI）后心肌细胞的丢失。然而，MSCs 在缺血性心脏病中的最佳治疗效果受到其存活率低和分化率低的限制。因此，提高 MSC 的存活率和分化率对于提高 MSCs 在 AMI 中的疗效是必要的和关键的。在本文中，从大鼠腹股沟脂肪组织中分离的 MSCs 被称为脂肪间充质干细胞（ASCs），并通过在 Transwell 系统中与心肌细胞共培养来预先指定第四代 ASCs（共 ASCs）。14 天后，通过细胞免疫荧光检测 GATA-4（一种转录因子）和心肌肌钙蛋白 I。在大鼠 AMI 产生后 24 小时内，阿托伐他汀（阿托伐他汀组）或载体（对照组）给药。14 天后，评估炎症参数和心功能。其余存活的大鼠分别注射总共 1×10(6)个共 ASCs/100 μl 磷酸缓冲盐水（PBS）、1×10(6)个 ASCs/100 μl PBS 或 100 μl PBS。细胞注射后 28 天，评估移植细胞的存活率、分化率和心功能。共 ASCs 中 GATA-4 表达的百分比为 28.5%±5.6%，心肌肌钙蛋白 I 的百分比为 22.8%±3.2%。与对照组相比，三个阿托伐他汀组的浸润性炎症细胞数量、髓过氧化物酶活性、炎症细胞因子（VCAM-1、TNF-α、Hs-CRP）mRNA 表达和 Bax 蛋白表达均显著降低，Bcl-2 蛋白表达和心功能显著改善（P<0.05）。与阿托伐他汀 2+ASCs 组和对照+共 ASCs 组相比，阿托伐他汀 3+共 ASCs 组的 4-6-二脒基-2-苯基吲哚染色细胞数量和心肌肌钙蛋白 I 阳性移植细胞数量以及心功能改善最为显著（P<0.05）。心脏环境的预先改善，结合 ASCs 的预先指定，有利于提高 ASCs 在 AMI 后改善心功能的治疗效果。
