A 3D Human Liver Model of Nonalcoholic Steatohepatitis
| العنوان: | A 3D Human Liver Model of Nonalcoholic Steatohepatitis |
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| المؤلفون: | Sandrine Roche, Zsolt Bocskei, Michel Didier, Anne-Céline Le Fèvre, Cécile Orsini, Lucile Hoet, Jean-Claude Guillemot, Tamara Slavnic, Corinne Rocher, Aimo Kannt, Xavier Vigé, Vincent Mikol, Marie-Dominique Bock, Agnès Jacquet, Gilles Haussy, Valérie Martin, Marion Duriez |
| المساهمون: | Publica |
| المصدر: | Journal of Clinical and Translational Hepatology |
| بيانات النشر: | XIA & HE Publishing Inc., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Nonalcoholic steatohepatitis, Cost effectiveness, 3d model, Bioinformatics, digestive system, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, medicine, Viability assay, Human primary cells, Hepatology, Human liver, business.industry, Chemistry, Liver cell, Disease progression, nutritional and metabolic diseases, medicine.disease, Key features of NASH, digestive system diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Hepatocyte, Cancer research, 030211 gastroenterology & hepatology, Tumor necrosis factor alpha, Original Article, Steatosis, Steatohepatitis, business, 3D liver model |
| الوصف: | Background and Aims: To better understand nonalcoholic steatohepatitis (NASH) disease progression and to evaluate drug targets and compound activity, we undertook the development of an in vitro 3D model to mimic liver architecture and the NASH environment. Methods: We have developed an in vitro preclinical 3D NASH model by coculturing primary human hepatocytes, human stellate cells, liver endothelial cells and Kupffer cells embedded in a hydrogel of rat collagen on a 96-well plate. A NASH-like environment was induced by addition of medium containing free fatty acids and tumor necrosis factor-α. This model was then characterized by biochemical, imaging and transcriptomics analyses. Results: We succeeded in defining suitable culture conditions to maintain the 3D coculture for up to 10 days in vitro, with the lowest level of steatosis and reproducible low level of inflammation and fibrosis. NASH disease was induced with a custom medium mimicking NASH features. The cell model exhibited the key NASH disease phenotypes of hepatocyte injury, steatosis, inflammation, and fibrosis. Hepatocyte injury was highlighted by a decrease of CYP3A4 expression and activity, without loss of viability up to day 10. Moreover, the model was able to stimulate a stable inflammatory and early fibrotic environment, with expression and secretion of several cytokines. A global gene expression analysis confirmed the NASH induction. Conclusions: This is a new in vitro model of NASH disease consisting of four human primary cell-types that exhibits most features of the disease. The 10-day cell viability and cost effectiveness of the model make it suitable for medium throughput drug screening and provide attractive avenues to better understand disease physiology and to identify and characterize new drug targets. |
| اللغة: | English |
| تدمد: | 2310-8819 2225-0719 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b28dbda09c771b8862ebc2d67273f4e6 http://europepmc.org/articles/PMC7782122 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b28dbda09c771b8862ebc2d67273f4e6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23108819 22250719 |
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