用人类胚胎干细胞衍生的心肌前体细胞进行治疗可改善心肌梗死后的心脏功能。
Treatment with hESC-Derived Myocardial Precursors Improves Cardiac Function after a Myocardial Infarction.
作者信息
Ye Jianqin, Gaur Meenakshi, Zhang Yan, Sievers Richard E, Woods Brandon J, Aurigui Julian, Bernstein Harold S, Yeghiazarians Yerem
机构信息
Department of Medicine, University of California San Francisco, San Francisco, California, 94143, United States of America.
Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, 94143, United States of America.
出版信息
PLoS One. 2015 Jul 31;10(7):e0131123. doi: 10.1371/journal.pone.0131123. eCollection 2015.
BACKGROUND
We previously reported the generation of a reporter line of human embryonic stem cells (hESCs) with enhanced green fluorescent protein (eGFP) expression driven by the α-myosin heavy chain (αMHC) promoter. The GFP+/αMHC+ cells derived from this cell line behave as multipotent, human myocardial precursors (hMPs) in vitro. In this study, we evaluated the therapeutic effects of GFP+/αMHC+ cells isolated from the reporter line in a mouse model of myocardial infarction (MI).
METHODS
MI was generated in immunodeficient mice. hMPs were injected into murine infarcted hearts under ultrasound guidance at 3 days post-MI. Human fetal skin fibroblasts (hFFs) were injected as control. Cardiac function was evaluated by echocardiography. Infarct size, angiogenesis, apoptosis, cell fate, and teratoma formation were analyzed by immunohistochemical staining.
RESULTS
Compared with control, hMPs resulted in improvement of cardiac function post-MI with smaller infarct size, induced endogenous angiogenesis, and reduced apoptosis of host cardiomyocytes at the peri-infarct zone at 28 days post-MI.
CONCLUSION
Intramyocardial injection of hMPs improved cardiac function post-MI. The engraftment rate of these cells in the myocardium post-MI was low, suggesting that the majority of effect occurs via paracrine mechanisms.
背景
我们之前报道了一种人类胚胎干细胞（hESCs）报告细胞系的构建，其增强型绿色荧光蛋白（eGFP）的表达由α-肌球蛋白重链（αMHC）启动子驱动。源自该细胞系的GFP+/αMHC+细胞在体外表现为多能的人类心肌前体细胞（hMPs）。在本研究中，我们评估了从报告细胞系分离的GFP+/αMHC+细胞在心肌梗死（MI）小鼠模型中的治疗效果。
方法
在免疫缺陷小鼠中制造MI。在MI后3天，在超声引导下将hMPs注射到小鼠梗死心脏中。注射人类胎儿皮肤成纤维细胞（hFFs）作为对照。通过超声心动图评估心脏功能。通过免疫组织化学染色分析梗死面积、血管生成、细胞凋亡、细胞命运和畸胎瘤形成。
结果
与对照组相比，hMPs使MI后心脏功能得到改善，梗死面积更小，诱导内源性血管生成，并在MI后28天时减少梗死周边区宿主心肌细胞的凋亡。
结论
心肌内注射hMPs改善了MI后的心脏功能。这些细胞在MI后心肌中的植入率较低，表明大部分作用是通过旁分泌机制发生的。
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