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Cell Transplant:羊膜上皮细胞EMT促进心脏再生

  1. 上皮间质转换
  2. 心肌再生
  3. 心脏

来源:生物谷 2013-12-25 21:15

2013年12月25日讯 /生物谷BIOON/--虽然基于干细胞的治疗方法已经显示出增强心肌再生功效,但自体(患者自捐赠)细胞只产生适度结果。近日,努力通过细胞移植来改善心肌的再生,来自德国的一个研究小组利用胎盘(羊膜上皮细胞AECs)上皮细胞,并将其转换成间充质细胞。

移栽转换成间充质状态的细胞到心肌梗死小鼠模型后,研究人员发现,上皮-间质转化(EMT)通过降低心肌梗死面积,能带来心肌再生益处。他们的结论是:EMT增强人羊膜上皮细胞的心脏保护作用。

这项研究将发表在Cell Transplantation杂志上。作者指出,羊膜上皮细胞已被证明具有多能细胞的特性,多能细胞能转化成其他类型的细胞。我们的假设是,EMT通过增加细胞流动性和细胞外基质调节能力,将提高羊膜上皮细胞的心肌再生能力。

事实上,老鼠心肌梗死建模四周后,用上皮-间质转化的羊膜上皮细胞治疗,小鼠心肌梗死面积明显减少。据研究人员介绍,由于EMT过程,羊膜上皮细胞失去了他们的“鹅卵石”结构,获得成纤维形状,该形状与一些生物的改变相关,最终帮助细胞获得流动性,并改变它们的分泌物。

在EMT-AEC(上皮-间质转化的羊膜上皮细胞)处理小鼠的一个直接结果是, EMT-AEC处理的心脏显示的更好的全局收缩功能,纵向应变率得到改善。研究人员补充说,虽然羊膜上皮细胞可能对心血管再生有帮助,但目前还不清楚羊膜上皮细胞得此功效是否需要“实际干性”或“多能性无关的分泌机制”。(生物谷Bioon.com)

 

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Epithelial‐to‐mesenchymal transition enhances the cardioprotective capacity of human amniotic epithelial cells

Roy R, Kukucka M, Messroghli D, Kunkel D, Brodarac A, Klose K, Geiβler S, Becher PM, Kang SK, Choi YH, Stamm C.

The amniotic epithelium consists of cells exhibiting mature epithelial cell characteristics but also varying degrees of stemness. We tested the hypothesis that induction of epithelial-tomesenchymal transition (EMT) in amniotic epithelial cells (AECs) derived from human placenta enhances their capacity to support the ischemic myocardium. In response to incubation with transforming growth factor-?1 protein (TGF-?1), AECs lost their cobblestone morphology and acquired a fibroblastoid shape, associated with downregulation of Ecadherin, upregulation of N-cadherin, Akt phosphorylation and intracellular periostin translocation. EMT-AECs displayed greatly enhanced mobility and secreted gelatinase activity as compared with na?ve AECs. The surface presentation of CD105 and CD73 decreased, and RNA microarray analysis mirrored the loss of epithelial characteristics and transcriptional profile. Unmodified AECs and EMT-AECs were then injected intramyocardially in fully immunocompetent mice after permanent LAD ligation, and heart function was followed by MRI as well as 2Dspeckle tracking echocardiography after 4 weeks. EMT-AEC-treated infarct hearts displayed better global systolic function and improved longitudinal strain rate in the area-of-interest (AOI). Although no signals of human cells were detectable by histology, infarct size was smaller in EMT-AEC-treated hearts, associated with fewer TUNEL positive cells and upregulation of periostin, while blood vessel density was increased in both, AEC and EMT-AEC-treated hearts. We conclude that EMT enhances the cardioprotective effects of human AECs.

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