Cytotoxicity Studies on 3D Primary Liver Microtissues using Operetta High Content Imaging System

ثبت نشده
چکیده

Liver toxicity remains one of the main reasons for drug failure in clinical trials. Improving preclinical toxicity testing is a major prerequisite for improving the drug de-risking process. Early compound de-risking decisions require in vitro data with the highest possible biological relevance. Three dimensional (3D) microtissues, or spheroids, are one of the most well characterized models for 3D culture and cell-based drug screening due to their reproducibility and similarity to the in vivo situation [Breslin and O’Driscoll, 2012]. Liver microtissues generated via the co-culture of primary human hepatocytes and non-parenchymal cells are used to better mimic the complex structure of human liver [Godoy et al., 2013].

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

High-content analysis of biomarker intensity and distribution in 3D microtissues

Three-dimensional (3D) cell culture methods are widely accepted as more physiologically relevant than conventional 2D cell culture methods and are believed to improve the prediction of drug candidates at an early stage of the drug development process. Here we describe the analysis of a spherical colon cancer microtissue model using the Operetta® High Content Imaging System. In vivo near-infrare...

متن کامل

A Multiparametric Live-Cell Cytotoxicity analysis using the Operetta

Cytotoxicity is a very complex process affecting multiple pathways. The ability to measure early indicators of toxicity is an essential part of drug discovery. An important approach to the detection of compound toxicity is a multiparametric analysis at the level of individual cells using High Content Analysis (HCA) applications [Abraham et al., 2008]. Such cell-based assays, which assess severa...

متن کامل

Micropatterned cell-cell interactions enable functional encapsulation of primary hepatocytes in hydrogel microtissues.

Drug-induced liver injury is a major cause of drug development failures and postmarket withdrawals. In vitro models that incorporate primary hepatocytes have been shown to be more predictive than model systems which rely on liver microsomes or hepatocellular carcinoma cell lines. Methods to phenotypically stabilize primary hepatocytes ex vivo often rely on mimicry of hepatic microenvironmental ...

متن کامل

Imaging Bile Canaliculi

Analyzing transport of biliary metabolites is essential to predict pharmacokinetics and hepatotoxicity during drug development. A functional impairment of hepatobilary transporters, such as bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP-2), is strongly associated with an increased risk of cholestatic liver injury. Currently, artificial models, such as BSEP expre...

متن کامل

High-Content, High-Throughput Screening for the Identification of Cytotoxic Compounds Based on Cell Morphology and Cell Proliferation Markers

Toxicity is a major cause of failure in drug discovery and development, and whilst robust toxicological testing occurs, efficiency could be improved if compounds with cytotoxic characteristics were identified during primary compound screening. The use of high-content imaging in primary screening is becoming more widespread, and by utilising phenotypic approaches it should be possible to incorpo...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2014