Natriuretic peptides in ectopic myocardial tissues originating from mouse embryonic stem cells

Natriuretic peptides in ectopic myocardial tissues originating from mouse embryonic stem cells
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DOI:
10.1002/jemt.20152
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发表时间:
2005-03-01
影响因子:
2.5
通讯作者:
Sasaki, K
Sasaki, K
中科院分区:
工程技术3区
文献类型:
--
作者:
Johkura, K;Cui, L;Sasaki, K

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在以前的报告中,我们描述了小鼠胚胎干细胞来源的心肌细胞在宿主腹膜后腔的存活和收缩功能。为了进一步了解胚胎干细胞来源的心肌细胞的性质,该研究评估了胚胎干细胞来源的异位心肌组织中利钠肽的合成。将胚状体中形成的心肌细胞移植到成年裸鼠的腹膜后腔中,并通过RT-PCR和免疫组织化学对发育的心肌组织进行心房肽和脑钠肽(ANP,BNP)的表征。在体外培养的胚状体中,通过RT-PCR检测ANP和BNP的基因表达,并通过光镜和电镜免疫细胞化学在少数心肌细胞中鉴定出肽阳性颗粒。移植后7天,移植物表现出多分化的畸胎瘤组织。心肌肌钙蛋白1、钙粘蛋白和连接蛋白43阳性的发育室心肌组织在移植物中是明显的,其中含有ANP阳性的心肌细胞。移植后30天观察有搏动束的移植物,其中检测两种利钠肽的基因表达。心肌组织中有丰富的心钠素免疫反应,以及与BNP免疫反应在较小程度上,是明显的移植。此外,还观察到无利钠肽免疫反应性的心肌组织。免疫电镜显示心肌细胞内含有ANP和/或BNP的分泌颗粒。这些结果表明,胚胎干细胞来源的异位心肌组织中的部分心肌细胞能够产生利钠肽,这表明它们可能被用作心脏激素的内分泌来源。(c)2005 Wiley-Liss,Inc.
In a previous report we described the survival and contractile function of mouse embryonic stem cell-derived cardiomyocytes in the host retroperitoneum. To further understand the nature of embryonic stem cell-derived cardiomyocytes, the study assessed the synthesis of natriuretic peptides in ectopic myocardial tissues of embryonic stem cell origin. Cardiomyocytes formed in embryoid body outgrowths were transplanted into the retroperitoneum of adult nude mice, and the myocardial tissues that developed were characterized by RT-PCR and immunohistochemistry concerning atrial and brain natriuretic peptides (ANP, BNP). In the outgrowths of embryoid bodies in vitro, gene expression of ANP and BNP was detected by RT-PCR and granules positive for the peptides were identified in a few cardiomyocytes by light and electron microscopic immunocytochemistry. Seven days after transplantation the transplants exhibited multidifferentiated teratoma tissues. Developing chamber myocardial tissues positive for cardiac troponin 1, cadherin, and connexin 43 were evident in the transplants, which contained ANP-positive cardiomyocytes. Transplants with beating bundles were observed 30 days after transplantation, in which gene expression of both natriuretic peptides was detected. Myocardial tissues with abundant ANP-immunoreactivity, as well as with BNP-immunoreactivity to a lesser extent, were evident in the transplants. Also, myocardial tissues without immunoreactivity for natriuretic peptides were observed. Immunoelectron microscopy showed discernible secretory granules containing ANP and/or BNP in the cardiomyocytes. These results showed that part of the cardiomyocytes in embryonic stem cell-derived ectopic myocardial tissues are capable of producing natriuretic peptides, which suggests that they may be used as an endocrine source for cardiac hormones. (c) 2005 Wiley-Liss, Inc.