基于微孔阵列的肝脂肪变性纤维化体外三维球体模型的疗效评价。

IF 4.1 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Jiamin Chen , Ping Wang , Zhanpeng Li , Jieyi Wu , Fang Tang , Niao Yang , Bohong Cen , Cuiyin Xie , Yufan Yang , Ziyan Yang , Chuwen Zhang , Xiangcao Yao , Zhongyuan Xu
{"title":"基于微孔阵列的肝脂肪变性纤维化体外三维球体模型的疗效评价。","authors":"Jiamin Chen ,&nbsp;Ping Wang ,&nbsp;Zhanpeng Li ,&nbsp;Jieyi Wu ,&nbsp;Fang Tang ,&nbsp;Niao Yang ,&nbsp;Bohong Cen ,&nbsp;Cuiyin Xie ,&nbsp;Yufan Yang ,&nbsp;Ziyan Yang ,&nbsp;Chuwen Zhang ,&nbsp;Xiangcao Yao ,&nbsp;Zhongyuan Xu","doi":"10.1016/j.jbiotec.2025.01.019","DOIUrl":null,"url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease worldwide, affecting more than 30 percent of adults. The most severe form of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), is characterized by necrotizing inflammation and rapid fibrosis progression, often leading to cirrhosis and hepatocellular carcinoma. Currently, only Resmetirom is approved for the treatment of MASH one of the main reasons is the absence of representative in vivo or in vitro models for MASH. To address this challenge, we developed a high-throughput 3D spheroid model consisting of human hepatocellular carcinoma cells (HepG2) and human hepatic stellate cells (LX-2) on microwell arrays. This model, induced with free fatty acids (FFA) to simulate steatosis and fibrosis, enables the assessment of efficacy and mechanisms for potential anti-MASH drugs. Our findings demonstrate that this in vitro spheroid model replicates key pathological features of human MASLD, including steatosis, oxidative stress, and fibrosis. Upon validation, we selected pirfenidone (PFD) and yinfenidone (AC-003), which are commonly used to treat idiopathic pulmonary fibrosis (IPF), to test their anti-MASH efficacy. Treatment with these drugs showed that they could regulate lipid synthesis and metabolism genes, reduce lipid accumulation, oxidative stress, and fibrosis levels. This 3D spheroid model represents a straightforward and efficient tool for screening anti-MASH drugs and investigating the molecular mechanisms of drug action.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"399 ","pages":"Pages 153-163"},"PeriodicalIF":4.1000,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"An in vitro 3D spheroid model with liver steatosis and fibrosis on microwell arrays for drug efficacy evaluation\",\"authors\":\"Jiamin Chen ,&nbsp;Ping Wang ,&nbsp;Zhanpeng Li ,&nbsp;Jieyi Wu ,&nbsp;Fang Tang ,&nbsp;Niao Yang ,&nbsp;Bohong Cen ,&nbsp;Cuiyin Xie ,&nbsp;Yufan Yang ,&nbsp;Ziyan Yang ,&nbsp;Chuwen Zhang ,&nbsp;Xiangcao Yao ,&nbsp;Zhongyuan Xu\",\"doi\":\"10.1016/j.jbiotec.2025.01.019\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease worldwide, affecting more than 30 percent of adults. The most severe form of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), is characterized by necrotizing inflammation and rapid fibrosis progression, often leading to cirrhosis and hepatocellular carcinoma. Currently, only Resmetirom is approved for the treatment of MASH one of the main reasons is the absence of representative in vivo or in vitro models for MASH. To address this challenge, we developed a high-throughput 3D spheroid model consisting of human hepatocellular carcinoma cells (HepG2) and human hepatic stellate cells (LX-2) on microwell arrays. This model, induced with free fatty acids (FFA) to simulate steatosis and fibrosis, enables the assessment of efficacy and mechanisms for potential anti-MASH drugs. Our findings demonstrate that this in vitro spheroid model replicates key pathological features of human MASLD, including steatosis, oxidative stress, and fibrosis. Upon validation, we selected pirfenidone (PFD) and yinfenidone (AC-003), which are commonly used to treat idiopathic pulmonary fibrosis (IPF), to test their anti-MASH efficacy. Treatment with these drugs showed that they could regulate lipid synthesis and metabolism genes, reduce lipid accumulation, oxidative stress, and fibrosis levels. This 3D spheroid model represents a straightforward and efficient tool for screening anti-MASH drugs and investigating the molecular mechanisms of drug action.</div></div>\",\"PeriodicalId\":15153,\"journal\":{\"name\":\"Journal of biotechnology\",\"volume\":\"399 \",\"pages\":\"Pages 153-163\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2025-01-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of biotechnology\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0168165625000252\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of biotechnology","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0168165625000252","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

代谢功能障碍相关脂肪变性肝病(MASLD)是目前世界上最常见的慢性肝病,影响超过30%的成年人。MASLD最严重的形式是代谢功能障碍相关脂肪性肝炎(MASH),其特征是坏死性炎症和快速纤维化进展,通常导致肝硬化和肝细胞癌。目前,只有雷司替龙被批准用于治疗MASH,主要原因之一是缺乏具有代表性的体内或体外模型。为了解决这一挑战,我们在微孔阵列上开发了由人肝癌细胞(HepG2)和人肝星状细胞(LX-2)组成的高通量3D球体模型。该模型由游离脂肪酸(FFA)诱导,模拟脂肪变性和纤维化,可用于评估潜在抗mash药物的疗效和机制。我们的研究结果表明,这种体外球形模型复制了人类MASLD的主要病理特征,包括脂肪变性、氧化应激和纤维化。在验证后,我们选择了常用的治疗特发性肺纤维化(IPF)的吡非尼酮(PFD)和英非尼酮(AC-003)来测试它们的抗mash效果。用这些药物治疗表明,它们可以调节脂质合成和代谢基因,减少脂质积累,氧化应激和纤维化水平。这种三维球体模型为筛选抗mash药物和研究药物作用的分子机制提供了一种简单有效的工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An in vitro 3D spheroid model with liver steatosis and fibrosis on microwell arrays for drug efficacy evaluation
Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease worldwide, affecting more than 30 percent of adults. The most severe form of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), is characterized by necrotizing inflammation and rapid fibrosis progression, often leading to cirrhosis and hepatocellular carcinoma. Currently, only Resmetirom is approved for the treatment of MASH one of the main reasons is the absence of representative in vivo or in vitro models for MASH. To address this challenge, we developed a high-throughput 3D spheroid model consisting of human hepatocellular carcinoma cells (HepG2) and human hepatic stellate cells (LX-2) on microwell arrays. This model, induced with free fatty acids (FFA) to simulate steatosis and fibrosis, enables the assessment of efficacy and mechanisms for potential anti-MASH drugs. Our findings demonstrate that this in vitro spheroid model replicates key pathological features of human MASLD, including steatosis, oxidative stress, and fibrosis. Upon validation, we selected pirfenidone (PFD) and yinfenidone (AC-003), which are commonly used to treat idiopathic pulmonary fibrosis (IPF), to test their anti-MASH efficacy. Treatment with these drugs showed that they could regulate lipid synthesis and metabolism genes, reduce lipid accumulation, oxidative stress, and fibrosis levels. This 3D spheroid model represents a straightforward and efficient tool for screening anti-MASH drugs and investigating the molecular mechanisms of drug action.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of biotechnology
Journal of biotechnology 工程技术-生物工程与应用微生物
CiteScore
8.90
自引率
2.40%
发文量
190
审稿时长
45 days
期刊介绍: The Journal of Biotechnology has an open access mirror journal, the Journal of Biotechnology: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. The Journal provides a medium for the rapid publication of both full-length articles and short communications on novel and innovative aspects of biotechnology. The Journal will accept papers ranging from genetic or molecular biological positions to those covering biochemical, chemical or bioprocess engineering aspects as well as computer application of new software concepts, provided that in each case the material is directly relevant to biotechnological systems. Papers presenting information of a multidisciplinary nature that would not be suitable for publication in a journal devoted to a single discipline, are particularly welcome.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信