Xue HY, Ren TY, Pan Q, Fan JG. Organoids as preclinical platforms for metabolic dysfunction-associated steatotic liver disease: Model construction, mechanistic dissection, and therapeutic translation. World J Gastroenterol 2026; 32(48): 123934 [DOI: 10.3748/wjg.123934]
Corresponding Author of This Article
Jian-Gao Fan, MD, PhD, Professor, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China. fanjiangao@xinhuamed.com.cn
Research Domain of This Article
Gastroenterology & Hepatology
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review-article
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Xue HY, Ren TY, Pan Q, Fan JG. Organoids as preclinical platforms for metabolic dysfunction-associated steatotic liver disease: Model construction, mechanistic dissection, and therapeutic translation. World J Gastroenterol 2026; 32(48): 123934 [DOI: 10.3748/wjg.123934]
World J Gastroenterol. Dec 28, 2026; 32(48): 123934 Published online Dec 28, 2026. doi: 10.3748/wjg.123934
Organoids as preclinical platforms for metabolic dysfunction-associated steatotic liver disease: Model construction, mechanistic dissection, and therapeutic translation
Hao-Yu Xue, Tian-Yi Ren, Qin Pan, Jian-Gao Fan
Hao-Yu Xue, Tian-Yi Ren, Qin Pan, Jian-Gao Fan, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Qin Pan, Jian-Gao Fan, Shanghai Institute of Pediatric Research, Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Author contributions: Xue HY conducted the literature review, did the analysis, created the artwork, and drafted the original manuscript; Ren TY and Pan Q assisted in manuscript supervision and made critical revisions; Fan JG conceptualized and designed the study, administered the project, supervised and reviewed the manuscript; all authors prepared the draft and approved the submitted version.
AI contribution statement: No AI tools were utilized for manuscript drafting, data analysis or figure preparation in this work.
Supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project, No. 023ZD0508700; the National Natural Science Foundation of China, No. 82470600; the Construction Project of the “Discipline Peak-Climbing Plan” of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. XKPF2024B401; and the Postdoctoral Research Startup Fund of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 2025BS02.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Jian-Gao Fan, MD, PhD, Professor, Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, China. fanjiangao@xinhuamed.com.cn
Received: June 3, 2026 Revised: July 30, 2026 Accepted: September 8, 2026 Published online: December 28, 2026 Processing time: 153 Days and 22.8 Hours
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global public health challenge, necessitating reliable in vitro models to unravel its complex pathophysiology and accelerate therapeutic development. Organoid systems have revolutionized MASLD research by recapitulating key hepatic structural features, cellular heterogeneity, and pathological processes. This review systematically summarizes liver organoids derived from human pluripotent stem cells, primary tissues, and immortalized cell lines in MASLD research, highlighting their distinct advantages in modeling MASLD pathogenesis, elucidating mechanisms, screening biomarkers, and validating therapeutics. In addition, we elaborate on the progress gained from multi-tissue organoid systems in deciphering inter-organ crosstalk and systemic metabolic perturbations associated with MASLD. We further discuss the inherent limitations of current organoid models and propose future directions for their development. Collectively, this review highlights the indispensable role of organoid models in unraveling the complex molecular mechanisms of MASLD, in advancing drug discovery, and in identifying diagnostic biomarkers, while also providing insights to accelerate their clinical translation toward precision medicine for MASLD.
Core Tip: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, yet targeted therapeutic options are limited. This review systematically summarizes liver organoids derived from human pluripotent stem cells, primary tissues, and immortalized cell lines in MASLD research, highlighting their distinct advantages in modeling MASLD pathogenesis, elucidating mechanisms, screening biomarkers, and validating therapeutics. It further discusses multi-tissue organoid systems, alongside current challenges and future directions to accelerate clinical translation and advance personalized medicine for MASLD.
