Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver models
The creation of ex vivo human liver models has long been a critical objective in academic, clinical, and pharmaceutical research, particularly for drug development, where accurate evaluation of hepatic metabolic dynamics is crucial. We have developed a bioengineered, perfused, organ-level human live...
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KeAi Communications Co., Ltd.
2025-01-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X24004328 |
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| author | Juan Liu Ariel Hanson Wenzhen Yin Qiao Wu Eliane Wauthier Jinmei Diao Timothy Dinh Jeff Macdonald Ruihong Li Masahiko Terajima Mitsuo Yamauchi Ziye Chen Praveen Sethupathy Jiahong Dong Lola M. Reid Yunfang Wang |
| author_facet | Juan Liu Ariel Hanson Wenzhen Yin Qiao Wu Eliane Wauthier Jinmei Diao Timothy Dinh Jeff Macdonald Ruihong Li Masahiko Terajima Mitsuo Yamauchi Ziye Chen Praveen Sethupathy Jiahong Dong Lola M. Reid Yunfang Wang |
| author_sort | Juan Liu |
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| description | The creation of ex vivo human liver models has long been a critical objective in academic, clinical, and pharmaceutical research, particularly for drug development, where accurate evaluation of hepatic metabolic dynamics is crucial. We have developed a bioengineered, perfused, organ-level human liver model that accurately replicates key liver functions, including metabolic activities, and protein synthesis, thus addressing some of the limitations associated with traditional liver monolayers, organoids, and matrix-embedded liver cells. Our approach utilizes liver-specific biomatrix scaffolds, prepared using an innovative protocol and fortified with matrix components that facilitate cellular interactions. These scaffolds, when seeded with human fetal liver cells or co-seeded with liver parenchymal and endothelial cell lines, enable the formation of three-dimensional (3D) human livers with enhanced cellular organization. The “recellularized tissue-engineered livers” (RCLs) have undergone various analyses, demonstrating the capability for establishing liver microenvironments ex vivo. Within 7–14 days, the RCLs exhibit evidence of liver differentiation and metabolic capabilities, underscoring the potential for use in drug metabolism and toxicity studies. Although our study represents a significant step forward, we acknowledge the need for direct comparisons with existing models and further research to fully elucidate the spectrum of regenerative responses. The high drug-metabolizing enzyme activity of RCLs, as demonstrated in our study, provides a promising avenue for investigating drug-induced liver injury mechanisms, contributing to a more detailed understanding of early drug discovery processes. |
| format | Article |
| id | doaj-art-99bd25e7d23342b3bdb50e7cb5adf686 |
| institution | OA Journals |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-99bd25e7d23342b3bdb50e7cb5adf6862025-08-20T02:23:45ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-01-014316218010.1016/j.bioactmat.2024.09.029Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver modelsJuan Liu0Ariel Hanson1Wenzhen Yin2Qiao Wu3Eliane Wauthier4Jinmei Diao5Timothy Dinh6Jeff Macdonald7Ruihong Li8Masahiko Terajima9Mitsuo Yamauchi10Ziye Chen11Praveen Sethupathy12Jiahong Dong13Lola M. Reid14Yunfang Wang15Hepato-pancreato-biliary Center, Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, China; Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 100084, ChinaDepartments of Biomedical Engineering, UNC School of Medicine, Chapel Hill, NC, 27599, USAHepato-pancreato-biliary Center, Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, ChinaInfection Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, ChinaDepartments of Cell Biology and Physiology, UNC School of Medicine, Chapel Hill, NC, 27599, USAHepato-pancreato-biliary Center, Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, China; Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 100084, ChinaDepartments of Genetics, UNC School of Medicine, Chapel Hill, NC, 27599, USADepartments of Biomedical Engineering, UNC School of Medicine, Chapel Hill, NC, 27599, USAHepato-pancreato-biliary Center, Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, ChinaOral and Craniofacial Health Sciences, UNC School of Dentistry, Chapel Hill, NC, 27599, USAOral and Craniofacial Health Sciences, UNC School of Dentistry, Chapel Hill, NC, 27599, USAHepato-pancreato-biliary Center, Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, ChinaDepartments of Genetics, UNC School of Medicine, Chapel Hill, NC, 27599, USA; Division of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USAHepato-pancreato-biliary Center, Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, China; Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 100084, ChinaDepartments of Biomedical Engineering, UNC School of Medicine, Chapel Hill, NC, 27599, USA; Program in Molecular Biology and Biotechnology, UNC School of Medicine, Chapel Hill, NC, 27599, USAHepato-pancreato-biliary Center, Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, China; Key Laboratory of Digital Intelligence Hepatology (Ministry of Education/Beijing), School of Clinical Medicine, Tsinghua University, Beijing, 100084, China; Corresponding author. Hepato-pancreato-biliary Center, Clinical Translational Science Center, Beijing Tsinghua Changgung Hospital, Tsinghua University, No.168 Litang Road, Changping District, Beijing, 102218, USA.The creation of ex vivo human liver models has long been a critical objective in academic, clinical, and pharmaceutical research, particularly for drug development, where accurate evaluation of hepatic metabolic dynamics is crucial. We have developed a bioengineered, perfused, organ-level human liver model that accurately replicates key liver functions, including metabolic activities, and protein synthesis, thus addressing some of the limitations associated with traditional liver monolayers, organoids, and matrix-embedded liver cells. Our approach utilizes liver-specific biomatrix scaffolds, prepared using an innovative protocol and fortified with matrix components that facilitate cellular interactions. These scaffolds, when seeded with human fetal liver cells or co-seeded with liver parenchymal and endothelial cell lines, enable the formation of three-dimensional (3D) human livers with enhanced cellular organization. The “recellularized tissue-engineered livers” (RCLs) have undergone various analyses, demonstrating the capability for establishing liver microenvironments ex vivo. Within 7–14 days, the RCLs exhibit evidence of liver differentiation and metabolic capabilities, underscoring the potential for use in drug metabolism and toxicity studies. Although our study represents a significant step forward, we acknowledge the need for direct comparisons with existing models and further research to fully elucidate the spectrum of regenerative responses. The high drug-metabolizing enzyme activity of RCLs, as demonstrated in our study, provides a promising avenue for investigating drug-induced liver injury mechanisms, contributing to a more detailed understanding of early drug discovery processes.http://www.sciencedirect.com/science/article/pii/S2452199X24004328Human tissue engineered liverLiver biomatrix scaffoldsMetabolismDrug-induced liver injury |
| spellingShingle | Juan Liu Ariel Hanson Wenzhen Yin Qiao Wu Eliane Wauthier Jinmei Diao Timothy Dinh Jeff Macdonald Ruihong Li Masahiko Terajima Mitsuo Yamauchi Ziye Chen Praveen Sethupathy Jiahong Dong Lola M. Reid Yunfang Wang Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver models Bioactive Materials Human tissue engineered liver Liver biomatrix scaffolds Metabolism Drug-induced liver injury |
| title | Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver models |
| title_full | Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver models |
| title_fullStr | Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver models |
| title_full_unstemmed | Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver models |
| title_short | Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver models |
| title_sort | decellularized liver scaffolds for constructing drug metabolically functional ex vivo human liver models |
| topic | Human tissue engineered liver Liver biomatrix scaffolds Metabolism Drug-induced liver injury |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X24004328 |
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