Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Ying, Shi, Qiong, Peng, Qi, Gao, Yue, Yang, Ting, Cheng, Yu, Wang, Hao, Luo, Yetao, Huang, Ailong, He, Tong-Chuan, Fan, Jiaming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
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
_version_ 1783456656801136640
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
work_keys_str_mv AT zhuying asimplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT shiqiong asimplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT pengqi asimplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT gaoyue asimplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT yangting asimplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT chengyu asimplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT wanghao asimplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT luoyetao asimplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT huangailong asimplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT hetongchuan asimplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT fanjiaming asimplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT zhuying simplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT shiqiong simplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT pengqi simplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT gaoyue simplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT yangting simplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT chengyu simplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT wanghao simplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT luoyetao simplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT huangailong simplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT hetongchuan simplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies
AT fanjiaming simplified3dlivermicrospheretissueculturemodelforhepaticcellsignalinganddruginducedhepatotoxicitystudies