Advanced 3D bioprinted liver models with human-induced hepatocytes for personalized toxicity screening
The development of advanced in vitro models for assessing liver toxicity and drug responses is crucial for personalized medicine and preclinical drug development. 3D bioprinting technology provides opportunities to create human liver models that are suitable for conducting high-throughput screening...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2025-01-01
|
| Series: | Journal of Tissue Engineering |
| Online Access: | https://doi.org/10.1177/20417314241313341 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841525308514107392 |
|---|---|
| author | Yue Ma Runbang He Bo Deng Miaomiao Luo Wenjie Zhang Lina Mao Wenxiang Hu Yilei Mao Huayu Yang Pengyu Huang |
| author_facet | Yue Ma Runbang He Bo Deng Miaomiao Luo Wenjie Zhang Lina Mao Wenxiang Hu Yilei Mao Huayu Yang Pengyu Huang |
| author_sort | Yue Ma |
| collection | DOAJ |
| description | The development of advanced in vitro models for assessing liver toxicity and drug responses is crucial for personalized medicine and preclinical drug development. 3D bioprinting technology provides opportunities to create human liver models that are suitable for conducting high-throughput screening for liver toxicity. In this study, we fabricated a humanized liver model using human-induced hepatocytes (hiHeps) derived from human fibroblasts via a rapid and efficient reprogramming process. These hiHeps were then employed in 3D bioprinted liver models with bioink materials that closely mimic the natural extracellular matrix. The constructed humanized 3D bioprinted livers (h3DPLs) exhibited mature hepatocyte functions, including albumin expression, glycogen storage, and uptake/release of indocyanine green and acetylated low-density lipoprotein. Notably, h3DPLs demonstrated increased sensitivity to hepatotoxic agents such as acetaminophen (APAP), making them a promising platform for studying drug-induced liver injury. Furthermore, our model accurately reflected the impact of rifampin, a cytochrome P450 inducer, on CYP2E1 levels and APAP hepatotoxicity. These results highlight the potential of hiHep-based h3DPLs as a cost-effective and high-performance alternative for personalized liver toxicity screening and preclinical drug testing, paving the way for improved drug development strategies and personalized therapeutic interventions. |
| format | Article |
| id | doaj-art-8783f20e180946f68e6302a3df2c81c5 |
| institution | Kabale University |
| issn | 2041-7314 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Journal of Tissue Engineering |
| spelling | doaj-art-8783f20e180946f68e6302a3df2c81c52025-01-17T15:03:30ZengSAGE PublishingJournal of Tissue Engineering2041-73142025-01-011610.1177/20417314241313341Advanced 3D bioprinted liver models with human-induced hepatocytes for personalized toxicity screeningYue Ma0Runbang He1Bo Deng2Miaomiao Luo3Wenjie Zhang4Lina Mao5Wenxiang Hu6Yilei Mao7Huayu Yang8Pengyu Huang9Engineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Institutes of Health Science, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaEngineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Institutes of Health Science, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaEngineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Institutes of Health Science, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaEngineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Institutes of Health Science, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaEngineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Institutes of Health Science, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaEngineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Institutes of Health Science, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaDepartment of Basic Research, Guangzhou National Laboratory, Guangdong, ChinaDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaDepartment of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, ChinaEngineering Research Center of Pulmonary and Critical Care Medicine Technology and Device (Ministry of Education), Tianjin Institutes of Health Science, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaThe development of advanced in vitro models for assessing liver toxicity and drug responses is crucial for personalized medicine and preclinical drug development. 3D bioprinting technology provides opportunities to create human liver models that are suitable for conducting high-throughput screening for liver toxicity. In this study, we fabricated a humanized liver model using human-induced hepatocytes (hiHeps) derived from human fibroblasts via a rapid and efficient reprogramming process. These hiHeps were then employed in 3D bioprinted liver models with bioink materials that closely mimic the natural extracellular matrix. The constructed humanized 3D bioprinted livers (h3DPLs) exhibited mature hepatocyte functions, including albumin expression, glycogen storage, and uptake/release of indocyanine green and acetylated low-density lipoprotein. Notably, h3DPLs demonstrated increased sensitivity to hepatotoxic agents such as acetaminophen (APAP), making them a promising platform for studying drug-induced liver injury. Furthermore, our model accurately reflected the impact of rifampin, a cytochrome P450 inducer, on CYP2E1 levels and APAP hepatotoxicity. These results highlight the potential of hiHep-based h3DPLs as a cost-effective and high-performance alternative for personalized liver toxicity screening and preclinical drug testing, paving the way for improved drug development strategies and personalized therapeutic interventions.https://doi.org/10.1177/20417314241313341 |
| spellingShingle | Yue Ma Runbang He Bo Deng Miaomiao Luo Wenjie Zhang Lina Mao Wenxiang Hu Yilei Mao Huayu Yang Pengyu Huang Advanced 3D bioprinted liver models with human-induced hepatocytes for personalized toxicity screening Journal of Tissue Engineering |
| title | Advanced 3D bioprinted liver models with human-induced hepatocytes for personalized toxicity screening |
| title_full | Advanced 3D bioprinted liver models with human-induced hepatocytes for personalized toxicity screening |
| title_fullStr | Advanced 3D bioprinted liver models with human-induced hepatocytes for personalized toxicity screening |
| title_full_unstemmed | Advanced 3D bioprinted liver models with human-induced hepatocytes for personalized toxicity screening |
| title_short | Advanced 3D bioprinted liver models with human-induced hepatocytes for personalized toxicity screening |
| title_sort | advanced 3d bioprinted liver models with human induced hepatocytes for personalized toxicity screening |
| url | https://doi.org/10.1177/20417314241313341 |
| work_keys_str_mv | AT yuema advanced3dbioprintedlivermodelswithhumaninducedhepatocytesforpersonalizedtoxicityscreening AT runbanghe advanced3dbioprintedlivermodelswithhumaninducedhepatocytesforpersonalizedtoxicityscreening AT bodeng advanced3dbioprintedlivermodelswithhumaninducedhepatocytesforpersonalizedtoxicityscreening AT miaomiaoluo advanced3dbioprintedlivermodelswithhumaninducedhepatocytesforpersonalizedtoxicityscreening AT wenjiezhang advanced3dbioprintedlivermodelswithhumaninducedhepatocytesforpersonalizedtoxicityscreening AT linamao advanced3dbioprintedlivermodelswithhumaninducedhepatocytesforpersonalizedtoxicityscreening AT wenxianghu advanced3dbioprintedlivermodelswithhumaninducedhepatocytesforpersonalizedtoxicityscreening AT yileimao advanced3dbioprintedlivermodelswithhumaninducedhepatocytesforpersonalizedtoxicityscreening AT huayuyang advanced3dbioprintedlivermodelswithhumaninducedhepatocytesforpersonalizedtoxicityscreening AT pengyuhuang advanced3dbioprintedlivermodelswithhumaninducedhepatocytesforpersonalizedtoxicityscreening |