Three-Dimensional Organoids as a Model to Study Nonalcoholic Fatty Liver Disease

Yujin Park; Deepthi Thadasina; Ifeoluwa Bolujo; Abdulkadir Isidan; Arthur A. Cross-Najafi; Kevin Lopez; Ping Li; Andrew M. Dahlem; Lindsey Kennedy; Keisaku Sato; Heather Francis; Gianfranco Alpini; Wenjun Zhang; Burcin Ekser

doi:10.1055/a-1934-5588

Seminars in Liver Disease, Inhaltsverzeichnis

Semin Liver Dis 2022; 42(04): 423-433
DOI: 10.1055/a-1934-5588

Review Article

Three-Dimensional Organoids as a Model to Study Nonalcoholic Fatty Liver Disease

Yujin Park

¹Department of Surgery, Division of Transplant Surgery, Indiana University School of Medicine, Indianapolis, Indiana

,

Deepthi Thadasina

¹Department of Surgery, Division of Transplant Surgery, Indiana University School of Medicine, Indianapolis, Indiana

,

Ifeoluwa Bolujo

¹Department of Surgery, Division of Transplant Surgery, Indiana University School of Medicine, Indianapolis, Indiana

,

Abdulkadir Isidan

¹Department of Surgery, Division of Transplant Surgery, Indiana University School of Medicine, Indianapolis, Indiana

,

Arthur A. Cross-Najafi

¹Department of Surgery, Division of Transplant Surgery, Indiana University School of Medicine, Indianapolis, Indiana

,

Kevin Lopez

¹Department of Surgery, Division of Transplant Surgery, Indiana University School of Medicine, Indianapolis, Indiana

,

Ping Li

¹Department of Surgery, Division of Transplant Surgery, Indiana University School of Medicine, Indianapolis, Indiana

,

Andrew M. Dahlem

²Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, Indiana

,

Lindsey Kennedy

³Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, and Division of Research, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana

,

Keisaku Sato

³Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, and Division of Research, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana

,

Heather Francis

³Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, and Division of Research, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana

,

Gianfranco Alpini

³Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, and Division of Research, Richard L. Roudebush VA Medical Center, Indianapolis, Indiana

,

Wenjun Zhang ^*

¹Department of Surgery, Division of Transplant Surgery, Indiana University School of Medicine, Indianapolis, Indiana

,

Burcin Ekser ^*

¹Department of Surgery, Division of Transplant Surgery, Indiana University School of Medicine, Indianapolis, Indiana

› Institutsangaben

Abstract

Despite the rising prevalence of nonalcoholic fatty liver disease (NAFLD), the underlying disease pathophysiology remains unclear. There is a great need for an efficient and reliable “human” in vitro model to study NAFLD and the progression to nonalcoholic steatohepatitis (NASH), which will soon become the leading indication for liver transplantation. Here, we review the recent developments in the use of three-dimensional (3D) liver organoids as a model to study NAFLD and NASH pathophysiology and possible treatments. Various techniques that are currently used to make liver organoids are discussed, such as the use of induced pluripotent stem cells versus primary cell lines and human versus murine cells. Moreover, methods for inducing lipid droplet accumulation and fibrosis to model NAFLD are explored. Finally, the limitations specific to the 3D organoid model for NAFLD/NASH are reviewed, highlighting the need for further development of multilineage models to include hepatic nonparenchymal cells and immune cells. The ultimate goal is to be able to accurately recapitulate the complex liver microenvironment in which NAFLD develops and progresses to NASH.

Keywords

NAFLD - NASH - human liver organoids - 3D cell culture

Volltext

Referenzen

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