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移植的人羊膜上皮细胞在心肌梗死大鼠模型中分泌旁分泌促血管生成细胞因子。

Transplanted Human Amniotic Epithelial Cells Secrete Paracrine Proangiogenic Cytokines in Rat Model of Myocardial Infarction.

作者信息

Song Yi-Sun, Joo Hyun-Woo, Park In-Hwa, Shen Guang-Yin, Lee Yonggu, Shin Jeong Hun, Kim Hyuck, Shin Il-Seob, Kim Kyung-Soo

机构信息

Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea.

出版信息

Cell Transplant. 2015;24(10):2055-64. doi: 10.3727/096368914X685609. Epub 2014 Nov 21.

Abstract

Human amniotic epithelial cells (h-AECs) have been shown to differentiate into cardiomyocyte-like cells in vivo that can regenerate myocardial tissue and improve cardiac function in a rat model of myocardial infarction (MI). In this study, we investigated the paracrine factors released from h-AECs under hypoxic conditions to elucidate the possible mechanisms underlying this previously reported phenomenon of h-AEC-mediated cardiac repair. We used hypoxic cell culture conditions to simulate myocardial infarction in vitro. In comparison to normal conditions, we found that h-AECs secreted higher levels of several cytokines, including angiogenin (ANG), epidermal growth factor (EGF), interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. To determine whether transplanted h-AECs express these proangiogenic cytokines in vivo, we ligated the coronary artery of rats to cause MI and injected either h-AECs or saline into the infarcted area. We found that the infarct and border zones of rat myocardium treated with h-AECs had higher expression levels of the human-origin cytokines ANG, EGF, IL-6, and MCP-1 compared to the tissues of saline-treated rats. In conclusion, h-AECs secreted proangiogenic cytokines in a rat model of MI, which may suggest that the paracrine effect by h-AECs could regenerate myocardial tissue and improve cardiac function.

摘要

人羊膜上皮细胞(h-AECs)已被证明在体内可分化为心肌样细胞,能够在心肌梗死(MI)大鼠模型中再生心肌组织并改善心脏功能。在本研究中,我们调查了缺氧条件下人羊膜上皮细胞释放的旁分泌因子,以阐明先前报道的h-AEC介导的心脏修复现象背后的可能机制。我们使用缺氧细胞培养条件在体外模拟心肌梗死。与正常条件相比,我们发现h-AECs分泌了更高水平的几种细胞因子,包括血管生成素(ANG)、表皮生长因子(EGF)、白细胞介素(IL)-6和单核细胞趋化蛋白(MCP)-1。为了确定移植的h-AECs在体内是否表达这些促血管生成细胞因子,我们结扎大鼠冠状动脉以造成心肌梗死,并将h-AECs或生理盐水注入梗死区域。我们发现,与生理盐水处理的大鼠组织相比,h-AECs处理的大鼠心肌梗死和边界区域中人类来源的细胞因子ANG、EGF、IL-6和MCP-1的表达水平更高。总之,在心肌梗死大鼠模型中,h-AECs分泌促血管生成细胞因子,这可能表明h-AECs的旁分泌作用可以再生心肌组织并改善心脏功能。

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