Journal article
Bioprinting functional hepatocyte organoids derived from human chemically induced pluripotent stem cells to treat liver failure
Gut, v 74(7), pp 1150-1164
01 Jul 2025
PMID: 40032498
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background To treat liver failure, three-dimensional (3D) bioprinting is a promising technology used to construct hepatic tissue models. However, current research on bioprinting of hepatic tissue models primarily relies on conventional single-cell-based bioprinting, where individual functional hepatocytes are dispersed and isolated within hydrogels, leading to insufficient treatment outcomes due to inadequate cell functionality.Objective Here, we aim to bioprint a hepatic tissue model using functional hepatocyte organoids (HOs) and evaluate its liver-specific functions in vitro and in vivo.Design Human chemically induced pluripotent stem cells (hCiPSCs) were used as a robust and non-genome-integrative cell source to produce highly viable and functional HOs (hCiPSC-HOs). An oxygen-permeable microwell device was used to enhance oxygen supply, ensuring high cell viability and promoting hCiPSC-HOs maturation. To maintain the long-term biofunction of hCiPSC-HOs, spheroid-based bioprinting was employed to construct hepatic tissue models (3DP-HOs). 3DP-HOs were intraperitoneally implanted in mice with liver failure.Results 3DP-HOs demonstrated enhanced cell viability when compared with a model fabricated using single-cell-based bioprinting and exhibited gene profiles closely resembling hCiPSC-HOs while maintaining liver-specific functionality. Moreover, 3DP-HOs implantation significantly improved survival in mice with CCl4-induced acute-on-chronic liver failure and also Fah-/- mice with liver failure. 3DP-HOs significantly reduced liver injury, inflammation and fibrosis indices while promoting liver regeneration and biofunction expression.Conclusion Our bioprinted hepatic tissue model exhibits remarkable therapeutic efficacy for liver failure and holds great potential for clinical research in the field of liver regenerative medicine.
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Details
- Title
- Bioprinting functional hepatocyte organoids derived from human chemically induced pluripotent stem cells to treat liver failure
- Creators
- Guangya Li - Peking UniversityJianyu He - Tsinghua UniversityJihang Shi - Chinese PLA General HospitalXinyi Li - Peking UniversityLulu Liu - Peking UniversityXinlan Ge - Chinese PLA General HospitalWenhan Chen - Peking UniversityJun Jia - Changping Lab, Beijing, Peoples R ChinaJinlin Wang - Peking UniversityMing Yin - Beijing Vitalstar Biotechnol, Beijing, Peoples R ChinaYasuyuki Sakai - The University of TokyoWei Sun - Drexel UniversityHongkui Deng - Peking UniversityYuan Pang - Tsinghua University
- Publication Details
- Gut, v 74(7), pp 1150-1164
- Publisher
- Bmj Publishing Group
- Number of pages
- 15
- Grant note
- 20220484075 / Beijing Nova Program; Beijing Municipal Science & Technology Commission 2022ZLB004 / Tsinghua University Initiative Scientific Research Program; Tsinghua University Z231100007223006 / Beijing Science and Technology Plan B17026 / The 111 Project; Ministry of Education, China - 111 Project 2021YFF1201100 / National Key Research and Development Program of China; National Key Research & Development Program of China 2022NSCQ- LZX0326 / Natural Science Foundation of Chongqing Changping Laboratory 32270603; 32288102; 52175273; 52211540006; 52422508 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Mechanical Engineering and Mechanics
- Web of Science ID
- WOS:001436156700001
- Scopus ID
- 2-s2.0-86000138245
- Other Identifier
- 991022197306504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Gastroenterology & Hepatology