多囊性肝病
胆管上皮细胞
诱导多能干细胞
阿拉吉尔综合征
定向微分
肝病
疾病
生物
医学
药理学
内科学
胆汁淤积
胚胎干细胞
肝移植
移植
生物化学
基因
作者
Fotios Sampaziotis,Miguel Brito,Pedro Madrigal,Alessandro Bertero,Kourosh Saeb‐Parsy,Filipa Soares,Elisabeth Schrumpf,Espen Melum,Tom H. Karlsen,J. A. Bradley,William Gelson,Susan Davies,Alastair Baker,Arthur Kaser,Graeme Alexander,Nicholas R.F. Hannan,Ludovic Vallier
摘要
The study of biliary disease has been constrained by a lack of primary human cholangiocytes. Here we present an efficient, serum-free protocol for directed differentiation of human induced pluripotent stem cells into cholangiocyte-like cells (CLCs). CLCs show functional characteristics of cholangiocytes, including bile acids transfer, alkaline phosphatase activity, γ-glutamyl-transpeptidase activity and physiological responses to secretin, somatostatin and vascular endothelial growth factor. We use CLCs to model in vitro key features of Alagille syndrome, polycystic liver disease and cystic fibrosis (CF)-associated cholangiopathy. Furthermore, we use CLCs generated from healthy individuals and patients with polycystic liver disease to reproduce the effects of the drugs verapamil and octreotide, and we show that the experimental CF drug VX809 rescues the disease phenotype of CF cholangiopathy in vitro. Our differentiation protocol will facilitate the study of biological mechanisms controlling biliary development, as well as disease modeling and drug screening.
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