EMT增强人羊膜上皮细胞的心脏保护作用

在最近的Cell Transplantation杂志上发表的一项研究中，来自德国的研究人员，从胎盘中获取人羊膜上皮细胞，将其转化为间充质细胞。他们发现，在将转化的细胞移植到心脏梗死小鼠模型后，EMT能够通过降低梗死面积，有利于心脏的再生。

　　

生物通报道：以细胞为基础的疗法已经被证明能够增强心脏再生，但是自体（患者自身供体）细胞仅仅产生了“温和的结果”。为了通过细胞移植来促进心肌再生，来自德国的一个研究团队，从胎盘中获取上皮细胞（羊膜上皮细胞，或AECs），将其转化为间充质细胞。研究人员发现，在将转化的细胞移植到心肌梗死小鼠模型中后，上皮间质转化（epithelial-to-mesenchymal transition，EMT），能够通过降低梗死面积，有利于心脏的再生。他们推断，EMT增强了人类AECs的心脏保护作用。这项研究成果，将在近期的Cell Transplantation杂志上刊出。

该论文的作者指出，已有研究证明，AECs与能够转化为所有其它类型细胞的多能干细胞，共有一些特性，而且，它们的分离和AECs的临床级扩增是“相对简单的”。

本论文的通讯作者、德国柏林勃兰登堡再生疗法中心的Christof Stamm博士说：“我们的假设是，EMT通过提高上皮细胞的流动性和细胞外基质调节能力，将会提高羊膜上皮细胞的心脏再生能力。的确，心肌梗塞小鼠模型构成后采用EMT-AECs治疗四周之后，心肌梗死面积显著减少。”

根据研究人员称，作为EMT的结果，AECs丢失了其“鹅卵石”结构，获得了一个纤维样形状，这与一些生物学改变有关，这些改变最终将会有助于AECs的流动性和改变其分泌物。

EMT-AEC治疗的一个直接结果是，EMT-AEC治疗的心脏表现出“更好的整体收缩功能和关注区域的纵向应变率提高。”

研究人员补充道，虽然AECs可能在心血管再生领域内有用处，但是仍不明确是否这个有用性需要“真实的干性（stemness）”或“多能性无关的分泌机制。”

他们这样写道：“在AEC和EMT-AEC治疗的心脏中，血管密度都出现增加，因此，我们推断，EMT增强了人类AECs的心脏保护作用。”

犹他大学心血管再生医学部主任和Cell Transplantation的责任编辑Amit N. Patel博士称：“这项研究凸显了AECs如何作为一种可能有用的干细胞群体，可以通过转化（例如EMT，在移植之前）将其作用最大化。这已经在一个心肌梗死模型中得以证实，但是非常有必要开展进一步的研究工作，来确定是否这种转化也与其它疾病（和其它细胞类型）有关。”（生物通：王英）

生物通推荐原文摘要：
Epithelial‐to‐mesenchymal transition enhances the cardioprotective capacity of human amniotic epithelial cells
Abstract: 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-β1 protein (TGF-β1), 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 naïve 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.