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Journal article
Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure
Gut, v 70(3), pp 567-574
01 Mar 2021
PMID: 32434830
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Objective Shortage of organ donors, a critical challenge for treatment of end-stage organ failure, has motivated the development of alternative strategies to generate organs in vitro. Here, we aim to describe the hepatorganoids, which is a liver tissue model generated by three-dimensional (3D) bioprinting of HepaRG cells and investigate its liver functions in vitro and in vivo.
Design 3D bioprinted hepatorganoids (3DP-HOs) were constructed using HepaRG cells and bioink, according to specific 3D printing procedures. Liver functions of 3DP-HOs were detected after 7 days of differentiation in vitro, which were later transplanted into Fah-deficient mice. The in vivo liver functions of 3DP-HOs were evaluated by survival time and liver damage of mice, human liver function markers and human-specific debrisoquine metabolite production.
Results 3DP-HOs broadly acquired liver functions, such as ALBUMIN secretion, drug metabolism and glycogen storage after 7 days of differentiation. After transplantation into abdominal cavity of Fah(-/-)Rag2(-/-) mouse model of liver injury, 3DP-HOs further matured and displayed increased synthesis of liver-specific proteins. Particularly, the mice acquired human-specific drug metabolism activities. Functional vascular systems were also formed in transplanted 3DP-HOs, further enhancing the material transport and liver functions of 3DP-HOs. Most importantly, transplantation of 3DP-HOs significantly improved the survival of mice.
Conclusions Our results demonstrated a comprehensive proof of principle, which indicated that 3DP-HO model of liver tissues possessed in vivo hepatic functions and alleviated liver failure after transplantation, suggesting that 3D bioprinting could be used to generate human liver tissues as the alternative transplantation donors for treatment of liver diseases.
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Details
- Title
- Three-dimensional bioprinted hepatorganoids prolong survival of mice with liver failure
- Creators
- Huayu Yang - Peking Union Medical College HospitalLejia Sun - Peking Union Medical College HospitalYuan Pang - Tsinghua UniversityDandan Hu - Department of Liver SurgeryHaifeng Xu - Peking Union Medical College HospitalShuangshuang Mao - Biomanufacturing Center, Department of Mechanical EngineeringWenbo Peng - ShanghaiTech UniversityYanan Wang - Chinese Academy of Medical Sciences & Peking Union Medical CollegeYiyao Xu - Peking Union Medical College HospitalYong-Chang Zheng - PUMC & Chinese Acad Med Sci, Peking Union Med Coll PUMC Hosp, Dept Liver Surg, Beijing, Peoples R ChinaShunda Du - Peking Union Medical College HospitalHaitao Zhao - Peking Union Medical College HospitalTianyi Chi - Peking Union Medical College HospitalXin Lu - Peking Union Medical College HospitalXinting Sang - Peking Union Medical College HospitalShouxian Zhong - Peking Union Medical College HospitalXin Wang - Inner Mongolia UniversityHongbing Zhang - Chinese Academy of Medical Sciences & Peking Union Medical CollegePengyu Huang - School of Life Science and TechnologyWei Sun - Biomanufacturing Center, Department of Mechanical EngineeringYilei Mao - Peking Union Medical College Hospital
- Publication Details
- Gut, v 70(3), pp 567-574
- Publisher
- Bmj Publishing Group
- Number of pages
- 8
- Grant note
- 31970687; 31571509; 31522038; 51805294; 81730078 / National Natural Science Foundation of China (NSFC) B17026 / 111 Project; Ministry of Education, China - 111 Project ShanghaiTech start--up grant 2015CB553802 / National Basic Research Program of China 973 Program; National Basic Research Program of China 2016-I2M-1-001 / CAMS Innovation Fund for Medical Sciences (CIFMS) 2019YFA0801501; 2016YFA0100500 / Ministry of Science and Technology of China (MOST); Ministry of Science and Technology, China XDA15014300 / Strategic Priority Program (SPP) on Space Science 2015AA020303 / National High-tech Research and Development Projects (863) 2016YFE0107100 / International Science and Technology Projects
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Mechanical Engineering and Mechanics
- Web of Science ID
- WOS:000616739300017
- Scopus ID
- 2-s2.0-85100770615
- Other Identifier
- 991019167433804721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Gastroenterology & Hepatology