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人类肝脏组织三维空间分辨模型揭示NAFLD进展过程
作者:小柯机器人 发布时间:2019/12/4 16:30:25

德国马克斯·普朗克分子细胞生物学和遗传学研究所Marino Zerial、德累斯顿工业大学Jochen Hampe等研究人员合作解析了人类肝脏组织的三维空间分辨几何和功能模型,从而揭示了非酒精性脂肪肝疾病(NAFLD)进展的新方面。 这一研究成果于2019年12月2日在线发表在国际学术期刊《自然—医学》上。

研究人员应用了多光子成像、3D数字重建和计算仿真来生成NAFLD不同阶段的人类肝脏组织的空间分辨几何和功能模型。研究人员确定了一组与疾病进展相关的形态学细胞和组织参数,并在3D胆管网络中发现了明显的拓扑缺陷。个性化的胆汁液动力学模拟预测,胆道周围压力和微胆汁淤积会增加,这与患者血清中胆汁淤积生物标志物升高有关。这一人类肝脏组织空间分辨模型可以通过识别定量的多参数细胞和组织特征来定义疾病进展并提供有关NAFLD病理生理学的新见解。

据介绍,疾病的早期诊断是有效治疗疾病的关键。人活组织检查的组织病理学分析是诊断组织改变的金标准。但是,这种方法的分辨率较低,并且会忽略由于功能更改而导致的三维结构变化。

附:英文原文

Title: Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression

Author: Fabin Segovia-Miranda, Hernn Morales-Navarrete, Michael Kcken, Vincent Moser, Sarah Seifert, Urska Repnik, Fabian Rost, Mario Brosch, Alexander Hendricks, Sebastian Hinz, Christoph Rcken, Dieter Ltjohann, Yannis Kalaidzidis, Clemens Schafmayer, Lutz Brusch, Jochen Hampe, Marino Zerial

Issue&Volume: 2019-12-02

Abstract: Early disease diagnosis is key to the effective treatment of diseases. Histopathological analysis of human biopsies is the gold standard to diagnose tissue alterations. However, this approach has low resolution and overlooks 3D (three-dimensional) structural changes resulting from functional alterations. Here, we applied multiphoton imaging, 3D digital reconstructions and computational simulations to generate spatially resolved geometrical and functional models of human liver tissue at different stages of non-alcoholic fatty liver disease (NAFLD). We identified a set of morphometric cellular and tissue parameters correlated with disease progression, and discover profound topological defects in the 3D bile canalicular (BC) network. Personalized biliary fluid dynamic simulations predicted an increased pericentral biliary pressure and micro-cholestasis, consistent with elevated cholestatic biomarkers in patients’ sera. Our spatially resolved models of human liver tissue can contribute to high-definition medicine by identifying quantitative multiparametric cellular and tissue signatures to define disease progression and provide new insights into NAFLD pathophysiology.

DOI: 10.1038/s41591-019-0660-7

Source: https://www.nature.com/articles/s41591-019-0660-7

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex