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
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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

从3d培养的真皮成纤维细胞中自产脑样ECM可促进神经元的生长和存活
由于人脑的复杂性和原代神经细胞的有限可用性,体外研究神经系统疾病仍然具有挑战性。组织工程通过产生自产的细胞外基质(ECM)基质,使三维(3D)细胞培养系统的发展成为可能。与传统的单层培养相比,在这种ECM基质中培养细胞可以更有效地模拟生理条件。在这项研究中,我们分析了嵌入自产ECM的3D培养真皮成纤维细胞的蛋白质组和基质。有趣的是,在这个组织工程3D模型中,计算机分析预测了神经发生相关功能的强烈激活。我们发现,通常与神经元发育和维持相关的ECM蛋白也在真皮成纤维细胞中表达。真皮成纤维细胞与诱导多能干细胞(iPSC)衍生的运动神经元共培养显著地延长了培养时间,同时最大限度地减少了神经元的死亡,所有这些都不需要昂贵的培养基补充。此外,成纤维细胞条件培养基可提高神经元存活率。虽然我们证明了真皮成纤维细胞衍生的ECM提供了丰富的蛋白质基质和支持神经元生长和存活的信号分子,但ECM本身似乎不足以维持神经元网络。这些发现表明,3D培养的患者来源的真皮成纤维细胞产生了神经支持的微环境,可以作为一种具有成本效益和侵入性较小的替代脑活检来模拟复杂的神经系统疾病。这种方法为研究这种神经生长和存活以及探索神经系统疾病的治疗策略提供了一个有前途的平台。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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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.
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