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© 2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Liver organoids have been increasingly adopted as a critical in vitro model to study liver development and diseases. However, the pre‐vascularization of liver organoids without affecting liver parenchymal specification remains a long‐lasting challenge, which is essential for their application in regenerative medicine. Here, the large‐scale formation of pre‐vascularized human hepatobiliary organoids (vhHBOs) is presented without affecting liver epithelial specification via a novel strategy, namely nonparenchymal cell grafting (NCG). Endothelial and mesenchymal cells are grafted to human hepatobiliary organoids (hHBOs) at the different liver epithelial differentiation stages without supplementing with nonparenchymal culture medium and growth factors. Endothelial grafting at the stage of hepatic maturation offers an optimal integration efficiency compared to the stage of hepatic specification. Additionally, grafting with mesenchymal proves crucial in endothelial invading and sprouting into the liver epithelial cells during the establishment of vhHBOs. Ectopic liver implants into mice further displayed integration of vhHBOs into mice vascular networks. Notably, transplanted vhHBOs self‐organized into native liver tissue like hepatic zone and bile ducts, indicating their potential to regenerate damaged hepatic and bile duct tissues. It is believed that nonparenchymal cell grafting will offer a novel technical route to form a high‐fidelity complex in vitro model for tissue engineering and regenerative medicine.

Details

Title
High‐Throughput Formation of Pre‐Vascularized hiPSC‐Derived Hepatobiliary Organoids on a Chip via Nonparenchymal Cell Grafting
Author
Fan, Han 1   VIAFID ORCID Logo  ; Shang, Jia 2   VIAFID ORCID Logo  ; Li, Junbo 3 ; Yang, Bo 3 ; Zhou, Ding 1   VIAFID ORCID Logo  ; Jiang, Shanqing 1   VIAFID ORCID Logo  ; Fan, Yuhang 1   VIAFID ORCID Logo  ; Zhou, Ying 4 ; Wang, Yuwen 1   VIAFID ORCID Logo  ; Liu, Peidi 1   VIAFID ORCID Logo  ; Li, Changyong 5 ; Chen, Zhishui 3 ; Chen, Pu 6   VIAFID ORCID Logo 

 Tissue Engineering and Organ Manufacturing (TEOM) Lab, Department of Biomedical Engineering, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China 
 Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China 
 Key Laboratory of Organ Transplantation, Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 
 Research Center for Medicine and Structural Biology of Wuhan University, Wuhan University, Wuhan, Hubei, China 
 Department of Physiology, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, Hubei, China 
 Tissue Engineering and Organ Manufacturing (TEOM) Lab, Department of Biomedical Engineering, Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China, TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, China 
Section
Research Article
Publication year
2025
Publication date
Feb 1, 2025
Publisher
John Wiley & Sons, Inc.
e-ISSN
21983844
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3170006796
Copyright
© 2025. This work is published under http://creativecommons.org/licenses/by/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.