Epicardial cells of human adults can undergo an epithelial-to-mesenchymal transition and obtain characteristics of smooth muscle cells in vitro
Epicardial cells of human adults can undergo an epithelial-to-mesenchymal transition and obtain characteristics of smooth muscle cells in vitro
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DOI：
10.1634/stemcells.2006-0366
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发表时间：
2007-02-01
期刊：
影响因子：
5.2
通讯作者：
de Vries, Antoine A. F.
中科院分区：
文献类型：
--
作者：
van Tuyn, John;Atsma, Douwe E.;de Vries, Antoine A. F.
心肌和冠状动脉的发育都严重依赖于心外膜细胞。在心脏形态发生过程中，心外膜细胞亚群经历上皮间充质转化(EMT)并侵入心肌，分化为各种类型的细胞，包括冠状动脉平滑肌细胞、血管周围和心脏间质成纤维细胞。我们目前对心外膜内胚层移植和随后的心外膜衍生细胞(EPDCs)的了解主要来自对鸡和小鼠胚胎发育的研究。由于缺乏体外培养系统，人们对人EPDCs知之甚少。在这里，我们首次报道了成人原代心外膜细胞培养的建立，并描述了它们的免疫表型、转录组、转导能力和体外分化潜能。形态和β-连环蛋白染色模式的变化表明，人心外膜细胞在体外培养的早期自发地进行EMT。EMT后的细胞表面抗原谱与上皮下成纤维细胞相似，但只有EPDCs表达心脏标志物基因GATA4和心肌肌钙蛋白T。感染编码转录因子myocardin的腺病毒载体或经转化生长因子-β1或骨形态发生蛋白-2处理后，EPDCs具有平滑肌细胞的特征。此外，EPDCs在体外可以成骨，但不能形成脂肪细胞或内皮细胞。体外培养的成人心外膜细胞至少具有胚胎细胞的部分分化潜能，是探索这些细胞生物学特性和治疗潜力的良好模型系统。
Myocardial and coronary development are both critically dependent on epicardial cells. During cardiomorphogenesis, a subset of epicardial cells undergoes an epithelial-to-mesenchymal transition (EMT) and invades the myocardium to differentiate into various cell types, including coronary smooth muscle cells and perivascular and cardiac interstitial fibroblasts. Our current knowledge of epicardial EMT and the ensuing epicardium-derived cells (EPDCs) comes primarily from studies of chick and mouse embryonic development. Due to the absence of an in vitro culture system, very little is known about human EPDCs. Here, we report for the first time the establishment of cultures of primary epicardial cells from human adults and describe their immunophenotype, transcriptome, transducibility, and differentiation potential in vitro. Changes in morphology and beta-catenin staining pattern indicated that human epicardial cells spontaneously undergo EMT early during ex vivo culture. The surface antigen profile of the cells after EMT closely resembles that of subepithelial fibroblasts; however, only EPDCs express the cardiac marker genes GATA4 and cardiac troponin T. After infection with an adenovirus vector encoding the transcription factor myocardin or after treatment with transforming growth factor-beta 1 or bone morphogenetic protein-2, EPDCs obtain characteristics of smooth muscle cells. Moreover, EPDCs can undergo osteogenesis but fail to form adipocytes or endothelial cells in vitro. Cultured epicardial cells from human adults recapitulate at least part of the differentiation potential of their embryonic counterparts and represent an excellent model system to explore the biological properties and therapeutic potential of these cells.