Novel Vascularized Human Liver Organoids for Modeling Alcohol-Induced Liver Injury and Developing Hepatoprotective Therapy
文献类型：期刊论文
| 作者 | Yang, Kangdi1; Chu, Xiayan1; Wang, Xuerui1; Zhang, Wenkun1; Lu, Jinnuo1; Xu, Chuting1; Hu, Shoucheng1; Pan, Guoyu6; Yang, Chih-tsung5; Zhang, Xiaohui2 |
| 刊名 | ADVANCED SCIENCE
 |
| 出版日期 | 2025-12-05 |
| 页码 | 19 |
| 关键词 | alcoholic liver injury (ALI) drug screening liver organoids organoid therapy vascularization |
| DOI | 10.1002/advs.202511169 |
| 通讯作者 | Guo, Zhaobin(guozhaobin@shutcm.edu.cn) ; Liu, Hanyang(brandenliu@live.com) ; Ge, Guangbo(geguangbo@shutcm.edu.cn) |
| 英文摘要 | Liver organoids have emerged as transformative tools for disease modeling and therapy development. However, their inability to form functional multivascular networks significantly limits their capacity to replicate the multifaceted functions of the native human liver with high fidelity. Here, novel vascularized liver organoids (3HLOs) are constructed by co-culturing robust human reprogrammed hepatocyte-like cells (hrHLs) with endothelial cells (HUVECs) and mesenchymal stem cells (HUMSCs) in a 3D system. After optimization, 3HLOs form vascular architecture featuring CD31+ endothelial networks and CK19+ biliary ducts, while demonstrating enhanced hepatic function, including upregulated glycogen storage, elevated albumin secretion, accelerated indocyanine green uptake, and improved rhodamine-123 excretion. To improve physiological relevance, 3HLOs-on-chip models are developed for modeling alcohol-induced liver injury (ALI) pathogenesis and testing hepatoprotective agents. The in vitro findings closely match in vivo observations, confirming the high physiological relevance of 3HLOs-on-chip ALI models. Subcutaneous implantation of 3HLOs significantly attenuated liver injury and promoted hepatic regeneration in end-stage ALI mice, primarily through establishing functional anastomoses with host microvasculature. Multi-omics analysis revealed that 3HLOs secreted human hepatoprotective proteins into the host circulating system, thereby modulating inflammatory responses and lipid metabolism pathways. Collectively, this work offers a robust and reliable platform for ALI modeling, drug testing, and liver regeneration. |
| WOS关键词 | CELLS ; ALPHA-1-ANTITRYPSIN ; FAILURE ; HEPATOCYTES ; REGULATORS ; DISEASE ; REPAIR |
| 资助项目 | National Natural Science Foundation of China[U23A20516] ; National Natural Science Foundation of China[82304446] ; National Natural Science Foundation of China[82273897] ; National Natural Science Foundation of China[82104281] ; National Natural Science Foundation of China[82300730] ; Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine[2023YZZ02] ; Noncommunicable Chronic Diseases-National Science and Technology Major Project[2025ZD0546900] ; Key Laboratory[SHUTCM-SKL-202508] ; State Key Laboratory of Fine Chemicals, Dalian University of Technology[KF2202] ; State Key Laboratory of Fine Chemicals, Dalian University of Technology[KF2414] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001631031700001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322178]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Guo, Zhaobin; Liu, Hanyang; Ge, Guangbo |
| 作者单位 | 1.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai Frontiers Sci Ctr TCM Chem Biol, State Key Lab Discovery & Utilizat Funct Component, Shanghai 201203, Peoples R China 2.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China 3.Charite Univ Med Berlin, Dept Hepatol & Gastroenterol, Campus Virchow Klinikum, D-13353 Berlin, Germany 4.Charite Univ Med Berlin, Dept Hepatol & Gastroenterol, Campus Charite Mitte, D-13353 Berlin, Germany 5.Univ South Australia, Future Ind Inst, Mawson Lakes Campus, Adelaide, SA 5095, Australia 6.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yang, Kangdi,Chu, Xiayan,Wang, Xuerui,et al. Novel Vascularized Human Liver Organoids for Modeling Alcohol-Induced Liver Injury and Developing Hepatoprotective Therapy[J]. ADVANCED SCIENCE,2025:19. |
| APA | Yang, Kangdi.,Chu, Xiayan.,Wang, Xuerui.,Zhang, Wenkun.,Lu, Jinnuo.,...&Ge, Guangbo.(2025).Novel Vascularized Human Liver Organoids for Modeling Alcohol-Induced Liver Injury and Developing Hepatoprotective Therapy.ADVANCED SCIENCE,19. |
| MLA | Yang, Kangdi,et al."Novel Vascularized Human Liver Organoids for Modeling Alcohol-Induced Liver Injury and Developing Hepatoprotective Therapy".ADVANCED SCIENCE (2025):19. |
入库方式： OAI收割
来源：上海药物研究所
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