Self-assembling 3D vessel-on-chip model with hiPSC-derived astrocytes.

IF 5.9 2区 医学 Q1 CELL & TISSUE ENGINEERING
Stem Cell Reports Pub Date : 2024-07-09 Epub Date: 2024-06-13 DOI:10.1016/j.stemcr.2024.05.006
Dennis M Nahon, Marc Vila Cuenca, Francijna E van den Hil, Michel Hu, Tessa de Korte, Jean-Philippe Frimat, Arn M J M van den Maagdenberg, Christine L Mummery, Valeria V Orlova
{"title":"Self-assembling 3D vessel-on-chip model with hiPSC-derived astrocytes.","authors":"Dennis M Nahon, Marc Vila Cuenca, Francijna E van den Hil, Michel Hu, Tessa de Korte, Jean-Philippe Frimat, Arn M J M van den Maagdenberg, Christine L Mummery, Valeria V Orlova","doi":"10.1016/j.stemcr.2024.05.006","DOIUrl":null,"url":null,"abstract":"<p><p>Functionality of the blood-brain barrier (BBB) relies on the interaction between endothelial cells (ECs), pericytes, and astrocytes to regulate molecule transport within the central nervous system. Most experimental models for the BBB rely on freshly isolated primary brain cells. Here, we explored human induced pluripotent stem cells (hiPSCs) as a cellular source for astrocytes in a 3D vessel-on-chip (VoC) model. Self-organized microvascular networks were formed by combining hiPSC-derived ECs, human brain vascular pericytes, and hiPSC-derived astrocytes within a fibrin hydrogel. The hiPSC-ECs and pericytes showed close interactions, but, somewhat unexpectedly, addition of astrocytes disrupted microvascular network formation. However, continuous fluid perfusion or activation of cyclic AMP (cAMP) signaling rescued the vascular organization and decreased vascular permeability. Nevertheless, astrocytes did not affect the expression of proteins related to junction formation, transport, or extracellular matrix, indicating that, despite other claims, hiPSC-derived ECs do not entirely acquire a BBB-like identity in the 3D VoC model.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"946-956"},"PeriodicalIF":5.9000,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252484/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stem Cell Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.stemcr.2024.05.006","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/13 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
引用次数: 0

Abstract

Functionality of the blood-brain barrier (BBB) relies on the interaction between endothelial cells (ECs), pericytes, and astrocytes to regulate molecule transport within the central nervous system. Most experimental models for the BBB rely on freshly isolated primary brain cells. Here, we explored human induced pluripotent stem cells (hiPSCs) as a cellular source for astrocytes in a 3D vessel-on-chip (VoC) model. Self-organized microvascular networks were formed by combining hiPSC-derived ECs, human brain vascular pericytes, and hiPSC-derived astrocytes within a fibrin hydrogel. The hiPSC-ECs and pericytes showed close interactions, but, somewhat unexpectedly, addition of astrocytes disrupted microvascular network formation. However, continuous fluid perfusion or activation of cyclic AMP (cAMP) signaling rescued the vascular organization and decreased vascular permeability. Nevertheless, astrocytes did not affect the expression of proteins related to junction formation, transport, or extracellular matrix, indicating that, despite other claims, hiPSC-derived ECs do not entirely acquire a BBB-like identity in the 3D VoC model.

利用源自 hiPSC 的星形胶质细胞自组装三维片上血管模型。
血脑屏障(BBB)的功能依赖于内皮细胞(EC)、周细胞和星形胶质细胞之间的相互作用来调节中枢神经系统内的分子运输。大多数 BBB 实验模型都依赖于新鲜分离的原代脑细胞。在这里,我们探索了将人类诱导多能干细胞(hiPSCs)作为三维芯片上血管(VoC)模型中星形胶质细胞的细胞来源。在纤维蛋白水凝胶中,将hiPSC衍生的EC、人脑血管周细胞和hiPSC衍生的星形胶质细胞结合在一起,形成了自组织微血管网络。hiPSC-ECs 和周细胞表现出密切的相互作用,但有些出乎意料的是,星形胶质细胞的加入破坏了微血管网络的形成。然而,持续的液体灌注或环磷酸腺苷(cAMP)信号的激活可修复血管组织并降低血管通透性。然而,星形胶质细胞并没有影响与连接形成、运输或细胞外基质相关的蛋白质的表达,这表明,尽管有其他说法,但在三维VoC模型中,hiPSC衍生的EC并没有完全获得类似于BBB的特性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Stem Cell Reports
Stem Cell Reports CELL & TISSUE ENGINEERING-CELL BIOLOGY
CiteScore
10.50
自引率
1.70%
发文量
200
审稿时长
28 weeks
期刊介绍: Stem Cell Reports publishes high-quality, peer-reviewed research presenting conceptual or practical advances across the breadth of stem cell research and its applications to medicine. Our particular focus on shorter, single-point articles, timely publication, strong editorial decision-making and scientific input by leaders in the field and a "scoop protection" mechanism are reasons to submit your best papers.
×
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