A scalable and sensitive steatosis chip with long-term perfusion of in situ differentiated HepaRG organoids.

Biomaterials
Yao TengHanry Yu

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a significant liver disease without approved therapy, lacking human NAFLD models to aid drug development. Existing models are either under-performing or too complex to allow robust drug screening. Here we have developed a 100-well drug testing platform with improved HepaRG organoids formed with uniform size distribution, and differentiated in situ in a perfusion microfluidic device, SteatoChip, to recapitulate major NAFLD features. Compared with the pre-differentiated spheroids, the in situ differentiated HepaRG organoids with perfusion experience well-controlled chemical and mechanical microenvironment, and 3D cellular niche, to exhibit enhanced hepatic differentiation (albumin+ cells ratio: 66.2% in situ perfusion vs 46.1% pre-differentiation), enriched and uniform hepatocyte distribution in organoids, higher level of hepatocyte functions (5.2 folds in albumin secretion and 7.6 folds in urea synthesis), enhanced cell polarity and bile canaliculi structures. When induced with free fatty acid (FFA), cells exhibit significantly higher level of lipid accumulation (6.6 folds for in situ perfusion vs 4.4 folds for pre-differentiation), altered glucose regulation and reduced Akt phosphoryl...Continue Reading

References

Feb 27, 2001·Cell Motility and the Cytoskeleton·E S TzanakakisW S Hu
Jun 15, 2007·Laboratory Investigation; a Journal of Technical Methods and Pathology·Andrea De GottardiAntoine Hadengue
Feb 12, 2009·Journal of Gastroenterology and Hepatology·Matteo RicchiPaola Loria
May 13, 2010·Journal of Pharmacological and Toxicological Methods·Marc LübberstedtKatrin Zeilinger
Jan 25, 2011·Current Medicinal Chemistry·N C Chavez-TapiaC Tiribelli
Aug 11, 2011·PloS One·Katarina BlagovicJoel Voldman
May 10, 2012·Expert Opinion on Drug Metabolism & Toxicology·Tommy B AnderssonJohn Gerry Kenna
May 31, 2013·Comprehensive Physiology·Aleksandr Treyer, Anne Müsch
Jun 7, 2013·International Journal of Molecular Sciences·Giridhar Kanuri, Ina Bergheim
Jul 31, 2013·Comprehensive Physiology·James L Boyer
Mar 8, 2014·International Journal of Molecular Sciences·Fei ZhaoYutao Zhan
Jul 19, 2014·Science·Madeline A Lancaster, Juergen A Knoblich
Feb 19, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Pamela Bachour-El AzziAndré Guillouzo
May 6, 2015·World Journal of Hepatology·Shehab M Abd El-Kader, Eman M Salah El-Den Ashmawy
Jun 28, 2015·Journal of Hepatology·Paul Gissen, Irwin M Arias
Jul 15, 2015·Journal of Clinical and Experimental Hepatology·Narendra S ChoudharyArvinder S Soin
Jan 3, 2016·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Yichiro HiguchiHiroshi Suemizu
Feb 10, 2016·Integrative Biology : Quantitative Biosciences From Nano to Macro·JaeSeo LeeSang-Hoon Lee
Oct 16, 2016·Clinical and Translational Science·J E EdwardsD Shapiro
Oct 21, 2016·The Journal of Pathology·Jennie Ka Ching LauJun Yu
Dec 6, 2016·Experimental Cell Research·Anja ZeigererMarino Zerial
Jan 28, 2017·World Journal of Gastroenterology : WJG·Tomasz KostrzewskiDavid J Hughes
Jun 28, 2017·World Journal of Hepatology·Mark Benedict, Xuchen Zhang
Aug 7, 2017·Colloids and Surfaces. B, Biointerfaces·Christina McKee, G Rasul Chaudhry
Dec 17, 2017·Journal of Gastroenterology·Yoshio Sumida, Masashi Yoneda
Dec 29, 2017·Advanced Healthcare Materials·Sang Hun LeeLuke P Lee
Feb 13, 2018·Gastroenterology·Chen ChenBart Spee
Jul 3, 2018·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Joost BoeckmansRobim M Rodrigues
Jul 25, 2018·Methods in Cell Biology·Fan LeeHanry Yu
Sep 12, 2018·Lab on a Chip·Emanuel BergerJens C Schwamborn
Sep 27, 2018·Scientific Reports·Mikael KozyraMagnus Ingelman-Sundberg
Nov 12, 2018·Journal of Hepatology·Zobair M Younossi
Apr 4, 2019·Frontiers in Bioengineering and Biotechnology·Sergei Grebenyuk, Adrian Ranga
Jun 4, 2019·Cell Metabolism·Rie OuchiTakanori Takebe
Jun 7, 2019·Science·Beverly A Purnell, Marc Lavine
Jun 7, 2019·Science·Sunghee Estelle ParkDongeun Huh
Jul 14, 2019·Gut·Nicole PriorMeritxell Huch

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Related Feeds

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.