Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardiol performance in infrcted rat hearts
Transplantation of human embryonic stem cell-derived cardiomyocytes improves myocardiol performance in infrcted rat hearts
复制标题
DOI：
10.1016/j.jacc.2007.07.054
复制
发表时间：
2007-11-06
影响因子：
24
通讯作者：
Gepstein, Lior
中科院分区：
文献类型：
--
作者：
Caspi, Oren;Huber, Irit;Gepstein, Lior
目的评价人胚胎干细胞(HESCs)及其心肌细胞衍生物(HESCCms)在大鼠慢性心肌梗死模型中的植入和改善心肌功能的能力。背景细胞疗法是一种新的心肌修复治疗方法，但因缺乏人心肌细胞来源而受到阻碍。方法将免疫抑制的健康大鼠(冠脉结扎后7~10d)随机分为未分化hESCs、hESC-CMS、非心肌细胞hESC衍生物或生理盐水组。结果未分化的人胚胎干细胞移植后可形成畸胎瘤样结构。通过移植体外预分化的hESC-CMS可以防止这一现象。移植的心肌细胞存活、增殖、成熟、排列，并与宿主心肌组织形成缝隙连接。在功能上，注射生理盐水或非心肌细胞hESC衍生物的动物表现出显著的左室扩张和功能恶化，而移植hESC-CMS则减弱了这一重塑过程。因此，在生理盐水组和非心肌细胞组，损伤后基线短缩分数恶化了50%(从20+/-2%恶化到10+/-2%)和30%(20+/-2%到14+/-2%)，而在hESC-CM组改善了22%(21+/-2%到25+/-3%)。结论大鼠大面积心肌梗死后移植hESC-CMS可形成稳定的心肌移植物，减轻心肌重塑过程，改善心肌功能。这些发现突出了hESCs在心肌细胞治疗策略中的潜力。
Objectives We evaluated the ability of human embryonic stem cells (hESCs) and their cardiomyocyte derivatives (hESCCMs) to engraft and improve myocardial performance in the rat chronic infarction model.Background Cell therapy is emerging as a novel therapy for myocardial repair but is hampered by the lack of sources for human cardiomyocytes.Methods Immunosuppressed healthy and infarcted (7 to 10 days after coronary ligation) rat hearts were randomized to injection of undifferentiated hESCs, hESC-CMs, noncardiomyocyte hESC derivatives, or saline. Detailed histological analysis and sequential echocardiography were used to determine the structural and functional consequences of cell grafting.Results Transplantation of undifferentiated hESCs resulted in the formation of teratoma-like structures. This phenomenon was prevented by grafting of ex vivo pre-differentiated hESC-CMs. The grafted cardiomyocytes survived, proliferated, matured, aligned, and formed gap junctions with host cardiac tissue. Functionally, animals injected with saline or nonmyocyte hESC derivatives demonstrated significant left ventricular (LV) dilatation and functional deterioration, whereas grafting of hESC-CMs attenuated this remodeling process. Hence, post-injury baseline fractional shortening deteriorated by 50% (from 20 +/- 2% to 10 +/- 2%) and by 30% (20 +/- 2% to 14 +/- 2%) in the saline and nonmyocyte groups while improving by 22% (21 +/- 2% to 25 +/- 3%) in the hESC-CM group. Similarly, wall motion score index and LV diastolic dimensions were significantly lower in the hESC-CM animals.Conclusions Transplantation of hESC-CMs after extensive myocardial infarction in rats results in the formation of stable cardiomyocyte grafts, attenuation of the remodeling process, and functional benefit. These findings highlight the potential of hESCs for myocardial cell therapy strategies.