Human embryonic stem cell-derived cardiomyocytes engraft but do not alter cardiac remodeling after chronic infarction in rats

被引:128
作者
Fernandes, S. [1 ,2 ,3 ]
Naumova, A. V. [1 ,2 ,5 ]
Zhu, W. Z. [1 ,2 ,3 ]
Laflamme, M. A. [1 ,2 ,3 ]
Gold, J. [6 ]
Murry, C. E. [1 ,2 ,3 ,4 ]
机构
[1] Univ Washington, Ctr Cardiovasc Biol, Seattle, WA 98109 USA
[2] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98109 USA
[3] Univ Washington, Dept Pathol, Seattle, WA 98109 USA
[4] Univ Washington, Dept Bioengn, Seattle, WA 98109 USA
[5] Univ Washington, Dept Radiol, Seattle, WA 98109 USA
[6] Geron Corp, Menlo Pk, CA 94025 USA
关键词
Heart failure; Myocardial infarction; Ischemia; Cell transplantation; Stem cells; MYOCARDIAL-INFARCTION; PARACRINE MECHANISMS; TRANSPLANTATION; REPAIR; HEART; SURVIVAL; DELIVERY; THERAPY; PERFORMANCE; TISSUE;
D O I
10.1016/j.yjmcc.2010.09.008
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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 Published by Elsevier Ltd
引用
收藏
页码:941 / 949
页数:9
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