Human embryonic stem cell-derived cardiomyocytes engraft but do not alter cardiac remodeling after chronic infarction in rats.
Human embryonic stem cell-derived cardiomyocytes engraft but do not alter cardiac remodeling after chronic infarction in rats.
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DOI：
10.1016/j.yjmcc.2010.09.008
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发表时间：
2010-12
影响因子：
5
通讯作者：
Murry CE
中科院分区：
文献类型：
--
作者：
Fernandes S;Naumova AV;Zhu WZ;Laflamme MA;Gold J;Murry CE
先前的研究表明，在急性心肌梗死模型中，注射促生存鸡尾酒（PSC）的人胚胎干细胞来源的心肌细胞（hESC-CM）可以保留收缩功能。由于已确诊心力衰竭的患者也可能受益于细胞移植，因此我们评估了移植到慢性心肌梗死模型中的 hESC-CM 的生理效应。裸鼠缺血再灌注后1个月，心肌内注射hESC-CM和PSC。在细胞注射程序后 1、2 和 3 个月评估注射 hESC-CM 的大鼠的左心室功能，并与 3 个对照组（注射无血清培养基、仅 PSC 或 PSC 中非心脏人类细胞的大鼠）进行比较。 3 个月时的组织学显示，人类心肌细胞存活，肌节组织增多，并且仍在增殖。尽管植入成功，但超声心动图和 MRI 分析显示，在研究的任何时间点，这 4 组之间的左心室结构或功能没有显着差异，这表明人类心肌细胞不会影响慢性心肌梗死大鼠模型的心脏重塑。当注射到慢性梗塞模型中时，hESC-CM 可以与横纹心肌细胞一起移植、存活并形成移植物，其效果至少与之前在急性心肌梗塞模型中观察到的一样。然而，尽管hESC-CM移植可以减轻急性模型中心力衰竭的进展，但相同的hESC-CM注射方案不足以恢复心脏功能或改变慢性心肌梗死模型的不良重塑。
Previous studies indicated that, in an acute myocardial infarction model, human embryonic stem cell-derived cardiomyocytes (hESC-CM) injected with a pro-survival cocktail (PSC) can preserve contractile function. Because patients with established heart failure may also benefit from cell transplantation, we evaluated the physiological effects of hESC-CM transplanted into a chronic model of myocardial infarction. Intramyocardial injection of hESC-CM with PSC was performed in nude rats at 1 month following ischemia-reperfusion. The left ventricular function of hESC-CM injected rats was evaluated at 1, 2 and 3 months after the cell injection procedure and was compared to 3 control groups (rats injected with serum-free media, PSC-only, or non-cardiac human cells in PSC). Histology at 3 months revealed that human cardiomyocytes survive, develop increased sarcomere organization and are still proliferating. Despite successful engraftment, both echocardiography and MRI analyses showed no significant difference in left ventricular structure or function between these 4 groups at any time point of the study, suggesting that human cardiomyocytes do not affect cardiac remodeling in a rat model of chronic myocardial infarction. When injected into a chronic infarct model, hESC-CM can engraft, survive and form grafts with striated cardiomyocytes at least as well as was previously observed in an acute myocardial infarction model. However, although hESC-CM transplantation can attenuate the progression of heart failure in an acute model, the same hESC-CM injection protocol is insufficient to restore heart function or to alter adverse remodeling of a chronic myocardial infarction model.
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影响因子：
6
作者：
Laflamme, MA;Gold, J;Murry, CE
通讯作者：
Murry, CE
影响因子：
24
作者：
Caspi, Oren;Huber, Irit;Gepstein, Lior
通讯作者：
Gepstein, Lior
影响因子：
3.7
作者：
VAESSEN, LMB;BROEKHUIZEN, R;SCHUURMAN, HJ
通讯作者：
SCHUURMAN, HJ
DOI：
10.1073/pnas.0908381106
发表时间：
2009-09-29
影响因子：
11.1
作者：
Stevens, K. R.;Kreutziger, K. L.;Murry, C. E.
通讯作者：
Murry, C. E.
影响因子：
4.6
作者：
Sakakibara, Y;Tambara, K;Komeda, M
通讯作者：
Komeda, M