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人羊膜液来源的心肌细胞。

Cardiomyocytes Derived from Human Amniotic Fluids.

机构信息

Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini 31, 66100, Chieti, Italy.

Department of Neuroscience, Imaging e Clinical Scienes, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini 31, 66100, Chieti, Italy.

出版信息

Sci Rep. 2018 Aug 13;8(1):12028. doi: 10.1038/s41598-018-30537-z.

Abstract

Human amniotic fluid (hAF) cells share characteristics of both embryonic and adult stem cells. They proliferate rapidly and can differentiate into cells of all embryonic germ layers but do not form teratomas. Embryoid-bodies obtained from hAF have cardiac differentiation potential, but terminal differentiation to cardiomyocytes (CMs) has not yet been described. Our purpose was to promote cardiac differentiation in hAFcells. Cells were exposed to inducing factors for up to 15 days. Only the subset of hAF cells expressing the multipotency markers SSEA4, OCT4 and CD90 (AF cells) responded to the differentiation process by increasing the expression of the cardiac transcription factors Nkx2.5 and GATA4, sarcomeric proteins (cTnT, α-MHC, α-SA), Connexin43 and atrial and ventricular markers. Furthermore, differentiated cells were positive for the calcium pumps CACNA1C and SERCA2a, with approximately 30% of AF-derived CM-like cells responding to caffeine or adrenergic stimulation. Some spontaneous rare beating foci were also observed. In conclusion, we demonstrated that AF cells might differentiate toward the cardiac lineage giving rise to CM-like cells characterized by several cardiac-specific molecular, structural, and functional properties.

摘要

人羊水(hAF)细胞具有胚胎和成体干细胞的共同特征。它们增殖迅速,可分化为所有胚胎胚层的细胞,但不会形成畸胎瘤。从 hAF 获得的类胚体具有心脏分化潜能,但尚未描述其向心肌细胞(CMs)的终末分化。我们的目的是促进 hAF 细胞的心脏分化。细胞暴露于诱导因子长达 15 天。只有表达多能性标记物 SSEA4、OCT4 和 CD90(AF 细胞)的 hAF 细胞亚群通过增加心脏转录因子 Nkx2.5 和 GATA4、肌节蛋白(cTnT、α-MHC、α-SA)、Connexin43 和心房和心室标记物的表达来响应分化过程。此外,分化细胞对钙泵 CACNA1C 和 SERCA2a 呈阳性,大约 30%的 AF 衍生的 CM 样细胞对咖啡因或肾上腺素刺激有反应。还观察到一些自发的罕见搏动焦点。总之,我们证明了 AF 细胞可能向心脏谱系分化,产生具有几种心脏特异性分子、结构和功能特性的 CM 样细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5b6/6089907/76d1c47e0a8b/41598_2018_30537_Fig1_HTML.jpg

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