一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Theranostics >>article
Theranostics

Theranostics

IF: 13.3
Download PDF

Generation of hepatic spheroids using human hepatocyte-derived liver progenitor-like cells for hepatotoxicity screening

Published:18 September 2019 DOI: 10.7150/thno.34520
Zhen-yu Wang,?Wei-Jian Li,?Hong-Shu Jing,?M. Ding,?Gongbo Fu,?Tianjie Yuan,?Weijian Huang,?Mengjun Dai,?Dan Tang,?Min Zeng,?Yi Chen,?Hongdan Zhang,?Xuejing Zhu,?Yuan-yuan Peng,?Qigen Li,?Wei-Feng Yu,?Hexin Yan,?B. Zhai

Abstract

Rationale: The idiosyncratic drug-induced liver injury (iDILI) is a major cause of acute liver injury and a key challenge in late-stage drug development. Individual heterogeneity is considered to be an essential factor of iDILI. However, few in vitro model can predict heterogeneity in iDILI. We have previously shown that mouse and human hepatocytes can be converted to expandable liver progenitor-like cells in vitro (HepLPCs). However, the limited proliferation potential of human HepLPCs confines its industrial application. Here, we reported the generation of a novel hepatocyte model not only to provide unlimited cell sources for human hepatocytes but also to establish a tool for studying iDILI in vitro. Methods: Human primary hepatocytes were isolated by modified two-step perfusion technique. The chemical reprogramming culture condition together with gene-transfer were then used to generate the immortalized HepLPC cell lines (iHepLPCs). Growth curve, doubling time, and karyotype were analyzed to evaluate the proliferation characteristics of iHepLPCs. Modified Hepatocyte Maturation Medium and 3D spheroid culture were applied to re-differentiate iHepLPCs. Results: iHepLPCs exhibited efficient expansion for at least 40 population doublings, with a stable proliferative ability. They could easily differentiate back into metabolically functional hepatocytes in vitro within 10 days. Furthermore, under three-dimensional culture conditions, the formed hepatic spheroids showed multiple liver functions and toxicity profiles close to those of primary human hepatocytes. Importantly, we established a hepatocyte bank by generating a specific number of such cell lines. Screening for population heterogeneity allowed us to analyze the in vitro heterogeneous responses to hepatotoxicity induced by molecular targeted drugs. Conclusions: In light of the proliferative capacity and the heterogeneity they represented, these iHepLPCs cell lines may offer assistance in studying xenobiotic metabolism as well as liver diseases in vitro.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
DAPT 208255-80-5 C23H26F2N2O4 288 suppliers $6.00-$3658.00
DAPT 208255-80-5 C23H26F2N2O4 288 suppliers $6.00-$3658.00
DAPT 208255-80-5 C23H26F2N2O4 288 suppliers $6.00-$3658.00
DAPT 208255-80-5 C23H26F2N2O4 288 suppliers $6.00-$3658.00

Similar articles

IF:19.8

Generation of iPSC-derived human venous endothelial cells for the modeling of vascular malformations and drug discovery

Cell stem cell Zihang Pan, Qiyang Yao,etc Published: 22 November 2024
IF:1.3

Metabolism of (-)-fenchone by CYP2A6 and CYP2B6 in human liver microsomes.

Xenobiotica M Miyazawa, K Gyoubu,etc Published: 1 February 2007
IF:6.7

Phytochemicals: A potential next generation agent for radioprotection

Phytomedicine Bimal Prasad Jit , Subhaswaraj Pattnaik ,etc Published: 1 November 2022
金沙县| 小金县| 三穗县| 竹北市| 忻州市| 晋州市| 竹北市| 潮安县| 大余县| 项城市| 金山区| 于田县| 绥棱县| 扶绥县| 正定县| 大田县| 比如县| 永清县| 东台市| 洪湖市| 清镇市| 太和县| 延安市| 长治市| 汤原县| 邻水| 岫岩| 娱乐| 峨山| 皋兰县| 安塞县| 夹江县| 乡城县| 上林县| 绥化市| 油尖旺区| 历史| 林芝县| 兴业县| 桦南县| 林州市|