2. Academic Validation
  3. Generation and applications of an expandable and mature hiPSC-derived liver organoid

Generation and applications of an expandable and mature hiPSC-derived liver organoid

  • Acta Pharm Sin B. 2025 Dec;15(12):6382-6398. doi: 10.1016/j.apsb.2025.09.029.
Sen Liu 1 2 3,  Ze Wang 2 4,  Liuyang Zhu 5,  Libo Wang 2,  Tianyu Zhao 2,  Pinsheng Han 6,  Yongdeng Xu 2,  Long Yang 5,  Lei Hu 7,  Fengying Yan 2 4,  Xiaoliang Wang 2,  Tao Cui 2 8,  Chunli Li 3 1,  Baofeng Yang 1 9
Affiliations

Affiliations

  • 1 Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 2 State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Institute of Pharmaceutical Research, Tianjin 300301, China.
  • 3 School of Pharmacy, Shenzhen Technology University, Shenzhen 518118, China.
  • 4 Research Unit for Drug Metabolism, Chinese Academy of Medical Sciences, Beijing 100730, China.
  • 5 Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin 300192, China.
  • 6 Nankai University of Medicine College, Tianjin 300192, China.
  • 7 Tianjin Tiancheng New Drug Evaluation Co., Ltd., Tianjin 300301, China.
  • 8 Hefei Tianhui Biotechnology Co., Ltd., Hefei 231137, China.
  • 9 School of Pharmacy, Harbin Medical University, Harbin 150081, China.
PMID: 41477334 DOI: 10.1016/j.apsb.2025.09.029
Abstract

Organoids have emerged as a powerful tool for modeling liver diseases, drug screening, and personalized treatments. However, they have a limited capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we designed a novel method to efficiently and reproducibly establish a protocol for generating functionally mature SB-HEOs (SB431542/BMP4-hepatic endoderm organoids) from hiPSC-derived hepatic endoderm (HE) cells. The maturation of these organoids was confirmed through transcriptome analysis and functional expression detection. We extended this culture system to various biomedical applications. This system can be used to identify hepatotoxicity with DILI drugs, model disease using OA stress, metabolize drugs using liquid chromatography-tandem mass spectrometry, and repopulate FRG mice. These organoids have both expansion and maturation characteristics, high drug metabolism ability to prolong the survival of FRG mice, can accurately identify hepatotoxic and non-hepatotoxic drugs, and mimic metabolic dysfunction-associated steatotic liver disease. Thus, SB-HEO provide a new cellular system for toxicology testing, drug metabolism, modeling liver diseases, and regenerative medicine. Especially benefiting from the high expression of CYP450 activity, SB-HEO shows high potential in the fields of drug testing and regenerative medicine.

Keywords

Cytochrome P450; Drug metabolism; Human-induced pluripotent stem cells; Liver diseases; Liver organoid; Regenerative medicine; Signaling pathway; Toxicology testing.

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