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肝胆管系统中的干细胞:在健康、胆管疾病和胆管癌中的作用。

Biliary stem cells in health and cholangiopathies and cholangiocarcinoma.

机构信息

Department of Translational and Precision Medicine.

Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.

出版信息

Curr Opin Gastroenterol. 2024 Mar 1;40(2):92-98. doi: 10.1097/MOG.0000000000001005. Epub 2024 Feb 8.

Abstract

PURPOSE OF REVIEW

This review discusses evidence regarding progenitor populations of the biliary tree in the tissue regeneration and homeostasis, and the pathobiology of cholangiopathies and malignancies.

RECENT FINDINGS

In embryogenesis biliary multipotent progenitor subpopulation contributes cells not only to the pancreas and gall bladder but also to the liver. Cells equipped with a constellation of markers suggestive of the primitive endodermal phenotype exist in the peribiliary glands, the bile duct glands, of the intra- and extrahepatic bile ducts. These cells are able to be isolated and cultured easily, which demonstrates the persistence of a stable phenotype during in vitro expansion, the ability to self-renew in vitro, and the ability to differentiate between hepatocyte and biliary and pancreatic islet fates.

SUMMARY

In normal human livers, stem/progenitors cells are mostly restricted in two distinct niches, which are the bile ductules/canals of Hering and the peribiliary glands (PBGs) present inside the wall of large intrahepatic bile ducts. The existence of a network of stem/progenitor cell niches within the liver and along the entire biliary tree inform a patho-biological-based translational approach to biliary diseases and cholangiocarcinoma since it poses the basis to understand biliary regeneration after extensive or chronic injuries and progression to fibrosis and cancer.

摘要

目的综述

本综述讨论了胆管树祖细胞群体在组织再生和稳态、胆管疾病和恶性肿瘤的病理生物学中的证据。

最近的发现

在胚胎发生过程中,胆管多能祖细胞亚群不仅为胰腺和胆囊,而且为肝脏提供细胞。存在于胆管周围腺体、胆管腺体内和肝内外胆管中的标记物提示具有原始内胚层表型的细胞能够被轻易地分离和培养,这证明了在体外扩增过程中稳定表型的持续存在、体外自我更新的能力以及分化为肝细胞、胆管和胰岛命运的能力。

总结

在正常人类肝脏中,干细胞/祖细胞主要局限于两个不同的龛位,即 Hering 胆管小管/管腔和存在于大肝内胆管壁内的胆管周围腺体 (PBG)。肝内和整个胆管树中存在干细胞/祖细胞龛位网络,为胆管疾病和胆管癌提供了基于病理生物学的转化方法,因为它为理解广泛或慢性损伤后的胆管再生以及进展为纤维化和癌症奠定了基础。

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