Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction
Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction
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DOI：
10.1006/jmcc.2000.1391
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发表时间：
2001-07-01
影响因子：
5
通讯作者：
Leor, J
中科院分区：
文献类型：
--
作者：
Etzion, S;Battler, A;Leor, J
细胞移植已被认为是各种心肌疾病的未来治疗方法。然而，目前尚不清楚在缺血和再灌注、冷冻损伤或心肌病动物模型中获得的令人鼓舞的结果是否可以在永久性冠状动脉闭塞和广泛心肌梗死（MI）的情况下重现。分离胚胎心脏细胞并培养3天以确认存活力、形态并用BrdU或报告基因LacZ标记细胞。在广泛Nil后7天，将大鼠随机分配到心肌瘢痕中进行细胞（1.5 × 10（6））移植（n = 11）或培养基注射（n = 16）。在植入前和植入后53 ± 3天进行超声心动图研究，以评估左心室（IV）重塑和功能。在随访期间，细胞处理的大鼠与16只对照大鼠中的4只相比没有死亡率（P = 0.12）。移植后1周、4周和8周，用X-gal染色、BrdU和a-SMA免疫组化鉴定移植细胞。抗α-SMA，连接蛋白-43，快和慢肌球蛋白重链抗体显示，在10个11细胞处理的心脏移植在不同阶段的分化。然而，其中许多保持了胚胎表型，并通过瘢痕组织与宿主心肌分离。系列超声心动图研究显示，细胞移植可防止瘢痕变薄、IV扩张和功能障碍，而对照组动物出现瘢痕变薄、显著LV扩张伴LV收缩性进行性恶化。在大鼠模型中广泛NO后移植胚胎心肌细胞可减轻IV扩张、梗死变薄和心肌功能障碍。尽管如此，许多移植物仍然是孤立的，没有分化成成人表型，即使在移植后2个月进行研究。(C)北京：科学出版社.
Cell transplantation has been proposed as a future therapy for various myocardial diseases. It is unknown, however, whether the encouraging results obtained in animal models of ischemia and reperfusion, cryoinjury or cardiomyopathy can be reproduced in the setting of permanent coronary artery occlusion and extensive myocardial infarction (MI). Embryonic cardiac cells were isolated and cultured for 3 days to confirm viability, morphology and to label cells with BrdU or the reporter gene LacZ. Seven days after extensive Nil, rats were randomized to cell (1.5 x 10(6)) transplantation (n = 11) or culture medium injection (n = 16) into the myocardial scar. Echocardiography study was performed before and 53 +/- 3 days after implantation to assess left ventricular (IV) remodeling and function. During follow-up, there was no mortality among cell-treated rats v 4 of 16 control rats (P = 0.12). X-gal staining, BrdU and a-SMA immunohistochemistry identified the engrafted cells 1 week, 4 weeks and 8 weeks after transplantation, respectively. Antibodies against alpha -SMA, connexin-43, fast and slow myosin heavy chain revealed grafts in various stages of differentiation in 10 of 11 cell-treated hearts. Many of them, however, kept their embryonic phenotype and were isolated from the host myocardium by scar tissue. Serial echocardiography studies revealed that cell transplantation prevented scar thinning, IV dilatation and dysfunction while control animals developed scar thinning, significant LV dilatation accompanied by progressive deterioration in LV contractility. Transplantation of embryonic cardiomyocytes after extensive NO in a rat model attenuate IV dilatation, infarct thinning, and myocardial dysfunction. Still, many grafts remain isolated and do not differentiate into an adult phenotype, even when studied 2 months after grafting. (C) 2001 Academic Press.