2. Academic Validation
  3. Distinct Roles of Matrigel Enabled the Production of Expandable Hepatoblast and Polarized Hepatocyte Organoids from Human Embryonic Stem Cells under 3-Dimensional Suspension Conditions

Distinct Roles of Matrigel Enabled the Production of Expandable Hepatoblast and Polarized Hepatocyte Organoids from Human Embryonic Stem Cells under 3-Dimensional Suspension Conditions

  • Biomater Res. 2025 Nov 7:29:0280. doi: 10.34133/bmr.0280.
Haibin Wu 1 2 3,  Jue Wang 3,  Shoupei Liu 1 2 3,  Yiyu Wang 2 3,  Jinghe Xie 3 4,  Xueyan Zhang 2 3,  Shuai Zhang 5,  Weili Gu 5 6,  Yongjian Zhou 1,  Yuyou Duan 1 2 3 7 8
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, China.
  • 2 Laboratory of Stem Cells and Translational Medicine, Center for Medical Research on Innovation and Translation, Institute of Clinical Medicine, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, China.
  • 3 Laboratory of Stem Cells and Translational Medicine, Institute for Life Science, School of Medicine, South China University of Technology, Guangzhou 510006, China.
  • 4 School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China.
  • 5 Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou 510180, China.
  • 6 Surgical Department of Hepatobiliary Pancreas and Spleen, Affiliated Chinese Medicine Hospital at Tianhe Campus, Guangzhou Medical University, Guangzhou 510645, China.
  • 7 National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China.
  • 8 The Innovation Centre of Ministry of Education for Development and Diseases, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, China.
PMID: 41209312 DOI: 10.34133/bmr.0280
Abstract

The liver is essential for a range of metabolic functions, and recent advances in Organoid technology have enabled the development of various liver organoids. However, the challenges of replicating the in vivo microenvironment, particularly the extracellular matrix, remain important in liver Organoid culture. In this study, we explored the roles of Matrigel, a commonly used extracellular matrix component, in the expansion, polarization, and functional maturation of liver organoids derived from human embryonic stem cells (hESCs) under 3-dimensional suspension conditions. Using multiple assays, we demonstrated that a low concentration of Matrigel supported the efficient expansion of hESC-derived hepatoblast organoids by regulating Reactive Oxygen Species (ROS)-autophagy homeostasis through the inhibition of ROS-AMPK-mTOR-mediated excessive Autophagy. Moreover, Matrigel induced the polarization of mature hepatocyte organoids differentiated from hESC-derived expandable hepatoblast organoids via activation of the FAK-ERK-AMPK pathway under 3-dimensional suspension conditions. Our findings underscore the importance of Integrin signaling in hepatocyte Organoid culture and provide insights for the development of artificial, synthetic, bioactive hydrogels for the large-scale production of hepatocytes for clinical applications.

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