• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

染色质重塑剂曲古抑菌素A：成人骨髓来源的人间充质干细胞肝分化的关键因素。

Chromatin remodeling agent trichostatin A: a key-factor in the hepatic differentiation of human mesenchymal stem cells derived of adult bone marrow.

作者信息

Snykers Sarah, Vanhaecke Tamara, De Becker Ann, Papeleu Peggy, Vinken Mathieu, Van Riet Ivan, Rogiers Vera

机构信息

Dept. Toxicology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090, Brussels, Belgium.

出版信息

BMC Dev Biol. 2007 Apr 2;7:24. doi: 10.1186/1471-213X-7-24.

DOI:10.1186/1471-213X-7-24
PMID:17407549
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1852547/
Abstract

BACKGROUND

The capability of human mesenchymal stem cells (hMSC) derived of adult bone marrow to undergo in vitro hepatic differentiation was investigated.

RESULTS

Exposure of hMSC to a cocktail of hepatogenic factors [(fibroblast growth factor-4 (FGF-4), hepatocyte growth factor (HGF), insulin-transferrin-sodium-selenite (ITS) and dexamethasone)] failed to induce hepatic differentiation. Sequential exposure to these factors (FGF-4, followed by HGF, followed by HGF+ITS+dexamethasone), however, resembling the order of secretion during liver embryogenesis, induced both glycogen-storage and cytokeratin (CK)18 expression. Additional exposure of the cells to trichostatin A (TSA) considerably improved endodermal differentiation, as evidenced by acquisition of an epithelial morphology, chronological expression of hepatic proteins, including hepatocyte-nuclear factor (HNF)-3beta, alpha-fetoprotein (AFP), CK18, albumin (ALB), HNF1alpha, multidrug resistance-associated protein (MRP)2 and CCAAT-enhancer binding protein (C/EBP)alpha, and functional maturation, i.e. upregulated ALB secretion, urea production and inducible cytochrome P450 (CYP)-dependent activity.

CONCLUSION

hMSC are able to undergo mesenchymal-to-epithelial transition. TSA is hereby essential to promote differentiation of hMSC towards functional hepatocyte-like cells.

摘要

背景

研究了源自成人骨髓的人间充质干细胞（hMSC）在体外进行肝分化的能力。

结果

将hMSC暴露于一组肝源性因子[成纤维细胞生长因子-4（FGF-4）、肝细胞生长因子（HGF）、胰岛素-转铁蛋白-亚硒酸钠（ITS）和地塞米松]未能诱导肝分化。然而，按照这些因子在肝脏胚胎发生过程中的分泌顺序依次暴露（FGF-4，接着是HGF，然后是HGF+ITS+地塞米松），诱导了糖原储存和细胞角蛋白（CK）18表达。细胞进一步暴露于曲古抑菌素A（TSA）显著改善了内胚层分化，表现为获得上皮形态、肝脏蛋白的时序性表达，包括肝细胞核因子（HNF）-3β、甲胎蛋白（AFP）、CK18、白蛋白（ALB）、HNF1α、多药耐药相关蛋白（MRP）2和CCAAT增强子结合蛋白（C/EBP）α，以及功能成熟，即上调的ALB分泌、尿素生成和诱导型细胞色素P450（CYP）依赖性活性。

结论

hMSC能够经历间充质-上皮转变。在此，TSA对于促进hMSC向功能性肝细胞样细胞的分化至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/3eaec540e06b/1471-213X-7-24-10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/ce5eba70d1fc/1471-213X-7-24-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/a5ec7d131459/1471-213X-7-24-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/a92d35b098a2/1471-213X-7-24-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/ce5bfa2b578b/1471-213X-7-24-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/496f9dbf3e7b/1471-213X-7-24-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/b286ddd07865/1471-213X-7-24-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/bf5bebcd2a29/1471-213X-7-24-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/9571776862ce/1471-213X-7-24-8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/ef1392be88c4/1471-213X-7-24-9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/3eaec540e06b/1471-213X-7-24-10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/ce5eba70d1fc/1471-213X-7-24-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/a5ec7d131459/1471-213X-7-24-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/a92d35b098a2/1471-213X-7-24-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/ce5bfa2b578b/1471-213X-7-24-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/496f9dbf3e7b/1471-213X-7-24-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/b286ddd07865/1471-213X-7-24-6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/bf5bebcd2a29/1471-213X-7-24-7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/9571776862ce/1471-213X-7-24-8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/ef1392be88c4/1471-213X-7-24-9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/1852547/3eaec540e06b/1471-213X-7-24-10.jpg

相似文献

1
Chromatin remodeling agent trichostatin A: a key-factor in the hepatic differentiation of human mesenchymal stem cells derived of adult bone marrow.染色质重塑剂曲古抑菌素A：成人骨髓来源的人间充质干细胞肝分化的关键因素。
BMC Dev Biol. 2007 Apr 2;7:24. doi: 10.1186/1471-213X-7-24.
2
Sequential exposure to cytokines reflecting embryogenesis: the key for in vitro differentiation of adult bone marrow stem cells into functional hepatocyte-like cells.依次暴露于反映胚胎发生的细胞因子：成体骨髓干细胞体外分化为功能性肝样细胞的关键。
Toxicol Sci. 2006 Dec;94(2):330-41; discussion 235-9. doi: 10.1093/toxsci/kfl058. Epub 2006 Jul 13.
3
Differentiation of neonatal rat epithelial cells from biliary origin into immature hepatic cells by sequential exposure to hepatogenic cytokines and growth factors reflecting liver development.通过依次暴露于反映肝脏发育的肝源性细胞因子和生长因子，将新生大鼠胆管源性上皮细胞分化为未成熟肝细胞。
Toxicol In Vitro. 2007 Oct;21(7):1325-31. doi: 10.1016/j.tiv.2007.03.013. Epub 2007 Apr 4.
4
In vitro hepatic differentiation of human bone marrow mesenchymal stem cells under differential exposure to liver-specific factors.人骨髓间充质干细胞在不同暴露于肝脏特异性因子条件下的体外肝脏分化
Transl Res. 2009 Sep;154(3):122-32. doi: 10.1016/j.trsl.2009.05.007. Epub 2009 Jun 24.
5
Hepatic differentiation of human bone marrow-derived mesenchymal stem cells by tetracycline-regulated hepatocyte nuclear factor 3beta.通过四环素调控的肝细胞核因子3β诱导人骨髓间充质干细胞向肝细胞分化
Hepatology. 2008 Aug;48(2):597-606. doi: 10.1002/hep.22362.
6
[Hepatocyte growth factor and fibroblast growth factor-4-induced differentiation of human bone marrow mesenchymal stem cells into hepatocyte-like cells in vitro].[肝细胞生长因子和成纤维细胞生长因子-4诱导人骨髓间充质干细胞体外分化为肝样细胞]
Nan Fang Yi Ke Da Xue Xue Bao. 2006 Oct;26(10):1439-42.
7
Characterization and hepatic differentiation of skin-derived precursors from adult foreskin by sequential exposure to hepatogenic cytokines and growth factors reflecting liver development.通过顺序暴露于反映肝脏发育的肝生成细胞因子和生长因子来对成年包皮来源的皮肤前体细胞进行表征和肝分化。
Toxicol In Vitro. 2009 Dec;23(8):1522-7. doi: 10.1016/j.tiv.2009.08.014. Epub 2009 Aug 29.
8
Hepatocyte-like cells from directed differentiation of mouse bone marrow cells in vitro.体外定向分化小鼠骨髓细胞获得的肝细胞样细胞
Acta Pharmacol Sin. 2005 Apr;26(4):469-76. doi: 10.1111/j.1745-7254.2005.00093.x.
9
Comparison of in vitro hepatogenic differentiation potential between various placenta-derived stem cells and other adult stem cells as an alternative source of functional hepatocytes.比较不同胎盘来源干细胞与其他成体干细胞的体外肝向分化潜能，作为功能性肝细胞的替代来源。
Differentiation. 2012 Oct;84(3):223-31. doi: 10.1016/j.diff.2012.05.007. Epub 2012 Aug 10.
10
The effect of dimethyl sulfoxide on hepatic differentiation of mesenchymal stem cells.二甲基亚砜对间充质干细胞肝向分化的影响。
Artif Cells Nanomed Biotechnol. 2016;44(1):157-64. doi: 10.3109/21691401.2014.928778. Epub 2014 Jun 30.

引用本文的文献

1
Epigenetic memory as crucial contributing factor in directing the differentiation of human iPSC into pancreatic β-cells in vitro.表观遗传记忆作为体外引导人诱导多能干细胞分化为胰腺β细胞的关键促成因素。
Cell Tissue Res. 2025 Mar;399(3):267-276. doi: 10.1007/s00441-025-03952-8. Epub 2025 Jan 30.
2
High levels of histone acetylation modifications promote the formation of PGCs.高水平的组蛋白乙酰化修饰促进原始生殖细胞的形成。
Poult Sci. 2025 Feb;104(2):104763. doi: 10.1016/j.psj.2024.104763. Epub 2025 Jan 6.
3
Mechanisms of Action of Mesenchymal Stem Cells in Metabolic-Associated Fatty Liver Disease.

本文引用的文献

1
Trichostatin A, a critical factor in maintaining the functional differentiation of primary cultured rat hepatocytes.曲古抑菌素A，维持原代培养大鼠肝细胞功能分化的关键因素。
Toxicol Appl Pharmacol. 2007 Jan 1;218(1):64-71. doi: 10.1016/j.taap.2006.10.012. Epub 2006 Oct 25.
2
Differentiation of hepatocytoid cell induced from whole-bone-marrow method isolated rat myeloid mesenchymal stem cells.全骨髓法分离的大鼠骨髓间充质干细胞诱导生成肝样细胞的分化
World J Gastroenterol. 2006 Aug 14;12(30):4866-9. doi: 10.3748/wjg.v12.i30.4866.
3
Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers.
间充质干细胞在代谢相关脂肪性肝病中的作用机制
Stem Cells Int. 2023 Jan 6;2023:3919002. doi: 10.1155/2023/3919002. eCollection 2023.
4
Molecular Crosstalk between Chromatin Remodeling and Tumor Microenvironment in Multiple Myeloma.染色质重塑与多发性骨髓瘤肿瘤微环境的分子串扰。
Curr Oncol. 2022 Dec 5;29(12):9535-9549. doi: 10.3390/curroncol29120749.
5
The Role of Histone Acetylation in Mesenchymal Stem Cell Differentiation.组蛋白乙酰化在间充质干细胞分化中的作用
Chonnam Med J. 2022 Jan;58(1):6-12. doi: 10.4068/cmj.2022.58.1.6. Epub 2022 Jan 25.
6
A Critical Perspective on 3D Liver Models for Drug Metabolism and Toxicology Studies.药物代谢与毒理学研究中3D肝脏模型的批判性视角
Front Cell Dev Biol. 2021 Feb 22;9:626805. doi: 10.3389/fcell.2021.626805. eCollection 2021.
7
Effect of valproic acid on the hepatic differentiation of mesenchymal stem cells in 2D and 3D microenvironments.丙戊酸对二维和三维微环境中间充质干细胞肝向分化的影响。
Mol Cell Biochem. 2021 Feb;476(2):909-919. doi: 10.1007/s11010-020-03955-9. Epub 2020 Oct 27.
8
Mesenchymal Stem Cells as a Promising Cell Source for Integration in Novel In Vitro Models.间充质干细胞作为一种有前途的细胞来源，可整合到新型体外模型中。
Biomolecules. 2020 Sep 10;10(9):1306. doi: 10.3390/biom10091306.
9
Different approaches for transformation of mesenchymal stem cells into hepatocyte-like cells.不同方法将间充质干细胞转化为肝细胞样细胞。
Stem Cell Res Ther. 2020 Feb 7;11(1):54. doi: 10.1186/s13287-020-1555-8.
10
Control of mesenchymal stem cell biology by histone modifications.组蛋白修饰对间充质干细胞生物学特性的调控
Cell Biosci. 2020 Feb 3;10:11. doi: 10.1186/s13578-020-0378-8. eCollection 2020.
源自人间充质干细胞的肝细胞向小鼠肝脏的功能整合。
Gut. 2007 Mar;56(3):405-15. doi: 10.1136/gut.2005.090050. Epub 2006 Aug 23.
4
Sequential exposure to cytokines reflecting embryogenesis: the key for in vitro differentiation of adult bone marrow stem cells into functional hepatocyte-like cells.依次暴露于反映胚胎发生的细胞因子：成体骨髓干细胞体外分化为功能性肝样细胞的关键。
Toxicol Sci. 2006 Dec;94(2):330-41; discussion 235-9. doi: 10.1093/toxsci/kfl058. Epub 2006 Jul 13.
5
Inducing hepatic differentiation of human mesenchymal stem cells in pellet culture.在微球培养中诱导人间充质干细胞向肝分化
Biomaterials. 2006 Aug;27(22):4087-97. doi: 10.1016/j.biomaterials.2006.03.022. Epub 2006 Apr 17.
6
Trichostatin a enhances gap junctional intercellular communication in primary cultures of adult rat hepatocytes.曲古抑菌素A增强成年大鼠原代肝细胞培养物中的间隙连接细胞间通讯。
Toxicol Sci. 2006 Jun;91(2):484-92. doi: 10.1093/toxsci/kfj152. Epub 2006 Mar 10.
7
Fibroblast growth factor-4 and hepatocyte growth factor induce differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocytes.成纤维细胞生长因子-4和肝细胞生长因子诱导人脐带血间充质干细胞分化为肝细胞。
World J Gastroenterol. 2005 Dec 21;11(47):7461-5. doi: 10.3748/wjg.v11.i47.7461.
8
Liver-specific gene expression in mesenchymal stem cells is induced by liver cells.间充质干细胞中肝脏特异性基因的表达是由肝细胞诱导产生的。
World J Gastroenterol. 2005 Aug 7;11(29):4497-504. doi: 10.3748/wjg.v11.i29.4497.
9
Differential effects of histone deacetylase inhibitors in tumor and normal cells-what is the toxicological relevance?组蛋白去乙酰化酶抑制剂在肿瘤细胞和正常细胞中的差异效应——其毒理学相关性是什么？
Crit Rev Toxicol. 2005 Apr-May;35(4):363-78. doi: 10.1080/10408440590935639.
10
Rat bone marrow mesenchymal stem cells differentiate into hepatocytes in vitro.大鼠骨髓间充质干细胞在体外分化为肝细胞。
World J Gastroenterol. 2005 Jun 14;11(22):3479-84. doi: 10.3748/wjg.v11.i22.3479.