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A simplified 3D liver microsphere tissue culture model for hepatic cell signaling and drug-induced hepatotoxicity studies
Although a number of experimental models have been developed for liver research, each has its own advantages and disadvantages. The present study attempted to develop a simple and effective 3-dimensional mouse liver microsphere tissue culture (LMTC) model in vitro for the analysis of hepatic functio...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777685/ https://www.ncbi.nlm.nih.gov/pubmed/31485603 http://dx.doi.org/10.3892/ijmm.2019.4321 |
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author | Zhu, Ying Shi, Qiong Peng, Qi Gao, Yue Yang, Ting Cheng, Yu Wang, Hao Luo, Yetao Huang, Ailong He, Tong-Chuan Fan, Jiaming |
author_facet | Zhu, Ying Shi, Qiong Peng, Qi Gao, Yue Yang, Ting Cheng, Yu Wang, Hao Luo, Yetao Huang, Ailong He, Tong-Chuan Fan, Jiaming |
author_sort | Zhu, Ying |
collection | PubMed |
description | Although a number of experimental models have been developed for liver research, each has its own advantages and disadvantages. The present study attempted to develop a simple and effective 3-dimensional mouse liver microsphere tissue culture (LMTC) model in vitro for the analysis of hepatic functions. Hepatic characteristics and potential applications of this model were compared with that of mouse model in vivo and mouse primary hepatocytes in vitro. Using freshly-perfused mouse liver tissue passed through 80-mesh sift strainer (sift80), it was demonstrated that under the optimal culture conditions, the sift80 microsphere tissue cultured in 2% bovine calf serum medium remained viable with marked proliferating cell nuclear antigen and anti-Myc proto-oncogene protein expression, exhibited normal hepatic functions including indocyanine green (ICG) uptake/release and periodic acid-Schiff staining, and expressed hepatocyte-specific genes for up to 2 weeks. The microsphere tissue was responsive to bone morphogenic protein 9 (BMP9) stimulation leading to upregulation of downstream targets of BMP9 signaling. Furthermore, 3 commonly-used liver-damaging drugs were indicated to effectively inhibit hepatic ICG uptake, and induce the expression of hepatotoxicity-associated genes. Therefore, this simplified LMTC model may be a useful in vitro tissue culture model to investigate drug-induced liver injury and metabolism, and hepatocyte-based cell singling. |
format | Online Article Text |
id | pubmed-6777685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-67776852019-10-09 A simplified 3D liver microsphere tissue culture model for hepatic cell signaling and drug-induced hepatotoxicity studies Zhu, Ying Shi, Qiong Peng, Qi Gao, Yue Yang, Ting Cheng, Yu Wang, Hao Luo, Yetao Huang, Ailong He, Tong-Chuan Fan, Jiaming Int J Mol Med Articles Although a number of experimental models have been developed for liver research, each has its own advantages and disadvantages. The present study attempted to develop a simple and effective 3-dimensional mouse liver microsphere tissue culture (LMTC) model in vitro for the analysis of hepatic functions. Hepatic characteristics and potential applications of this model were compared with that of mouse model in vivo and mouse primary hepatocytes in vitro. Using freshly-perfused mouse liver tissue passed through 80-mesh sift strainer (sift80), it was demonstrated that under the optimal culture conditions, the sift80 microsphere tissue cultured in 2% bovine calf serum medium remained viable with marked proliferating cell nuclear antigen and anti-Myc proto-oncogene protein expression, exhibited normal hepatic functions including indocyanine green (ICG) uptake/release and periodic acid-Schiff staining, and expressed hepatocyte-specific genes for up to 2 weeks. The microsphere tissue was responsive to bone morphogenic protein 9 (BMP9) stimulation leading to upregulation of downstream targets of BMP9 signaling. Furthermore, 3 commonly-used liver-damaging drugs were indicated to effectively inhibit hepatic ICG uptake, and induce the expression of hepatotoxicity-associated genes. Therefore, this simplified LMTC model may be a useful in vitro tissue culture model to investigate drug-induced liver injury and metabolism, and hepatocyte-based cell singling. D.A. Spandidos 2019-11 2019-08-21 /pmc/articles/PMC6777685/ /pubmed/31485603 http://dx.doi.org/10.3892/ijmm.2019.4321 Text en Copyright: © Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Zhu, Ying Shi, Qiong Peng, Qi Gao, Yue Yang, Ting Cheng, Yu Wang, Hao Luo, Yetao Huang, Ailong He, Tong-Chuan Fan, Jiaming A simplified 3D liver microsphere tissue culture model for hepatic cell signaling and drug-induced hepatotoxicity studies |
title | A simplified 3D liver microsphere tissue culture model for hepatic cell signaling and drug-induced hepatotoxicity studies |
title_full | A simplified 3D liver microsphere tissue culture model for hepatic cell signaling and drug-induced hepatotoxicity studies |
title_fullStr | A simplified 3D liver microsphere tissue culture model for hepatic cell signaling and drug-induced hepatotoxicity studies |
title_full_unstemmed | A simplified 3D liver microsphere tissue culture model for hepatic cell signaling and drug-induced hepatotoxicity studies |
title_short | A simplified 3D liver microsphere tissue culture model for hepatic cell signaling and drug-induced hepatotoxicity studies |
title_sort | simplified 3d liver microsphere tissue culture model for hepatic cell signaling and drug-induced hepatotoxicity studies |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777685/ https://www.ncbi.nlm.nih.gov/pubmed/31485603 http://dx.doi.org/10.3892/ijmm.2019.4321 |
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