Self-Produced Brain-Like ECM From 3D-Cultured Dermal Fibroblasts Enhances Neuronal Growth and Survival

IF 3.2 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS
Vincent Roy, Isabella Bienjonetti, Alexandre Paquet, François Gros-Louis
{"title":"Self-Produced Brain-Like ECM From 3D-Cultured Dermal Fibroblasts Enhances Neuronal Growth and Survival","authors":"Vincent Roy,&nbsp;Isabella Bienjonetti,&nbsp;Alexandre Paquet,&nbsp;François Gros-Louis","doi":"10.1002/biot.202400594","DOIUrl":null,"url":null,"abstract":"<p>Studying neurological disorders in vitro remains challenging due to the complexity of the human brain and the limited availability of primary neural cells. Tissue engineering enables the development of three-dimensional (3D) cell culture systems by generating a self-produced extracellular matrix (ECM) substrate. Culturing cells within this ECM substrate is known to more effectively mimic physiological conditions compared to traditional monolayer cultures. In this study, we analyzed the proteome and matrisome of 3D cultured dermal fibroblasts embedded in a self-produced ECM. Interestingly, in silico analysis predicted strong activation of neurogenesis-associated functions in this tissue-engineered 3D model. We showed that ECM proteins typically linked to neuronal development and maintenance were also expressed by dermal fibroblasts. Coculturing dermal fibroblasts with induced pluripotent stem cell (iPSC)-derived motor neurons notably enabled long-lasting culture periods while minimizing neuronal death, all without the need for costly media supplements. Furthermore, fibroblast-conditioned media enhanced neuronal survival. Although we demonstrated that the dermal fibroblast-derived ECM provided a rich matrix of proteins and signaling molecules that support neuronal growth and survival, the ECM alone seems insufficient to sustain the neuronal networks. These findings suggest that 3D cultured patient-derived dermal fibroblasts generate a neuro-supportive microenvironment and could serve as a cost-effective and less invasive alternative to brain biopsies for modeling complex neurological disorders. This approach offers a promising platform for studying such neural growth and survival and exploring therapeutic strategies for neurological diseases.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"20 3","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biot.202400594","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biotechnology Journal","FirstCategoryId":"5","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/biot.202400594","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0

Abstract

Studying neurological disorders in vitro remains challenging due to the complexity of the human brain and the limited availability of primary neural cells. Tissue engineering enables the development of three-dimensional (3D) cell culture systems by generating a self-produced extracellular matrix (ECM) substrate. Culturing cells within this ECM substrate is known to more effectively mimic physiological conditions compared to traditional monolayer cultures. In this study, we analyzed the proteome and matrisome of 3D cultured dermal fibroblasts embedded in a self-produced ECM. Interestingly, in silico analysis predicted strong activation of neurogenesis-associated functions in this tissue-engineered 3D model. We showed that ECM proteins typically linked to neuronal development and maintenance were also expressed by dermal fibroblasts. Coculturing dermal fibroblasts with induced pluripotent stem cell (iPSC)-derived motor neurons notably enabled long-lasting culture periods while minimizing neuronal death, all without the need for costly media supplements. Furthermore, fibroblast-conditioned media enhanced neuronal survival. Although we demonstrated that the dermal fibroblast-derived ECM provided a rich matrix of proteins and signaling molecules that support neuronal growth and survival, the ECM alone seems insufficient to sustain the neuronal networks. These findings suggest that 3D cultured patient-derived dermal fibroblasts generate a neuro-supportive microenvironment and could serve as a cost-effective and less invasive alternative to brain biopsies for modeling complex neurological disorders. This approach offers a promising platform for studying such neural growth and survival and exploring therapeutic strategies for neurological diseases.

Abstract Image

求助全文
约1分钟内获得全文 求助全文
来源期刊
Biotechnology Journal
Biotechnology Journal Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
8.90
自引率
2.10%
发文量
123
审稿时长
1.5 months
期刊介绍: Biotechnology Journal (2019 Journal Citation Reports: 3.543) is fully comprehensive in its scope and publishes strictly peer-reviewed papers covering novel aspects and methods in all areas of biotechnology. Some issues are devoted to a special topic, providing the latest information on the most crucial areas of research and technological advances. In addition to these special issues, the journal welcomes unsolicited submissions for primary research articles, such as Research Articles, Rapid Communications and Biotech Methods. BTJ also welcomes proposals of Review Articles - please send in a brief outline of the article and the senior author''s CV to the editorial office. BTJ promotes a special emphasis on: Systems Biotechnology Synthetic Biology and Metabolic Engineering Nanobiotechnology and Biomaterials Tissue engineering, Regenerative Medicine and Stem cells Gene Editing, Gene therapy and Immunotherapy Omics technologies Industrial Biotechnology, Biopharmaceuticals and Biocatalysis Bioprocess engineering and Downstream processing Plant Biotechnology Biosafety, Biotech Ethics, Science Communication Methods and Advances.
×
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