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<p>Hepatic fibrosis (HF) is a common and pivotal pathological stage in the progression of various chronic liver diseases, characterized by excessive deposition of extracellular matrix (ECM) due to aberrant activation of hepatic stellate cells (HSCs). Traditional research models are limited by species differences and oversimplified microenvironments, failing to meet the demands of precision medicine. Organoid technology, as an emerging three-dimensional (3D) culture system, can closely recapitulate the structural and functional complexity of the human liver, providing a revolutionary tool for HF research. This review systematically summarized the construction strategies and applications of HF organoids. Firstly, the key components and dynamic changes in the HF microenvironment were analyzed. Secondly, organoids derived from primary cells versus stem cells were compared. Thirdly, the methods for constructing fibrotic organoids via cytokine induction, pathological simulation, and genetic engineering were elaborated. Finally, the value and challenges of these models in mechanistic studies, drug screening, and regenerative medicine were discussed. Evidence indicated that multilineage liver organoids can recapitulate the complex interaction network of “hepatocytes-non-parenchymal cells-ECM”, providing a highly physiologically relevant platform for elucidating fibrosis mechanisms and developing targeted drugs. Although further optimization in maturation and standardization is needed, HF organoid technology holds great potential to bridge basic research and clinical translation, thereby accelerating the innovation of diagnostic and therapeutic strategies for HF.</p>

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Liver organoids: a novel platform for mechanistic research and drug screening in anti-liver fibrosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月4日

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  • Dongning Shen,
  • Shouhai Wu,
  • Xinhao Xue,
  • Menglin Huang,
  • Chunhe Wei,
  • Ting Fu,
  • Fan Wu,
  • Bo Liu,
  • Fangfang Xu

摘要

Hepatic fibrosis (HF) is a common and pivotal pathological stage in the progression of various chronic liver diseases, characterized by excessive deposition of extracellular matrix (ECM) due to aberrant activation of hepatic stellate cells (HSCs). Traditional research models are limited by species differences and oversimplified microenvironments, failing to meet the demands of precision medicine. Organoid technology, as an emerging three-dimensional (3D) culture system, can closely recapitulate the structural and functional complexity of the human liver, providing a revolutionary tool for HF research. This review systematically summarized the construction strategies and applications of HF organoids. Firstly, the key components and dynamic changes in the HF microenvironment were analyzed. Secondly, organoids derived from primary cells versus stem cells were compared. Thirdly, the methods for constructing fibrotic organoids via cytokine induction, pathological simulation, and genetic engineering were elaborated. Finally, the value and challenges of these models in mechanistic studies, drug screening, and regenerative medicine were discussed. Evidence indicated that multilineage liver organoids can recapitulate the complex interaction network of “hepatocytes-non-parenchymal cells-ECM”, providing a highly physiologically relevant platform for elucidating fibrosis mechanisms and developing targeted drugs. Although further optimization in maturation and standardization is needed, HF organoid technology holds great potential to bridge basic research and clinical translation, thereby accelerating the innovation of diagnostic and therapeutic strategies for HF.