Generation of decellularized human brain tissue for investigating cell-matrix interactions: a proof-of-concept study.

IF 4.8 3区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Frontiers in Bioengineering and Biotechnology Pub Date : 2025-06-05 eCollection Date: 2025-01-01 DOI:10.3389/fbioe.2025.1578467

Roemel Jeusep Bueno, Camila Fernández-Zapata, Maren Salla, Juliana Campo Garcia, Aylin Alacam, Oliver Klein, Chotima Böttcher, Helena Radbruch, Friedemann Paul, Sarah C Starossom, Rafaela V Silva, Carmen Infante-Duarte

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引用次数: 0

Abstract

The brain extracellular matrix (ECM) regulates myelin repair and regeneration following a demyelinating event by interacting with neuronal progenitors and immune cells. Therefore, generation and characterization of decellularized human brain tissue (DHBT) in regions with distinct neuroregenerative capacities are essential to determine factors modulating the cellular regenerative behavior. We have established an effective decellularization protocol for the human neural stem cell (NSC)-rich subventricular zone (SVZ) as well as, frontal cortex (FC) and white matter (WM), and defined region-specific matrisomes with comparative proteomics. Subsequently, as proof-of-concept, survival and differentiation of NSCs and monocytes within the DHBT were investigated. The proteomic analysis of the DHBT confirmed the retention of matrisome proteins such as COL4A1, FBB, NCAN, ANXA2. Unique to the SVZ were LGI3 and C1QB, while annexins, S100A and TGM2 were found in FC; S100B was exclusive to the WM. NSCs cultured within WM and FC acquired an astrocytic phenotype, but both astrocytic and oligodendrocytic phenotypes were promoted by the SVZ DHBT. Moreover, imaging mass cytometry analysis indicated an anti-inflammatory phenotype differentiation of monocytes seeded on SVZ and WM. Thus, the established model is suitable for investigation of ECM properties and assessment of cell-matrix interactions.

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用于研究细胞-基质相互作用的去细胞化人脑组织的产生：一项概念验证研究。

脑细胞外基质（ECM）通过与神经元祖细胞和免疫细胞相互作用，调节脱髓鞘事件后的髓磷脂修复和再生。因此，在具有不同神经再生能力的区域产生和表征脱细胞人脑组织（DHBT）对于确定调节细胞再生行为的因素至关重要。我们建立了一个有效的人类神经干细胞(NSC)-富脑室下区（SVZ），额叶皮层（FC）和白质（WM）脱细胞方案，并定义了区域特异性基质与比较蛋白质组学。随后，作为概念验证，研究了DHBT中NSCs和单核细胞的存活和分化。DHBT的蛋白质组学分析证实了COL4A1、FBB、NCAN、ANXA2等基质蛋白的保留。SVZ中有LGI3和C1QB， FC中有annexin、S100A和TGM2；S100B是WM独有的。在WM和FC中培养的NSCs获得星形细胞表型，但SVZ DHBT均促进星形细胞和少突胶质细胞表型。此外，成像细胞计数分析显示SVZ和WM上的单核细胞具有抗炎表型分化。因此，所建立的模型适用于研究ECM特性和评估细胞-基质相互作用。

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来源期刊

Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering

CiteScore

8.30

自引率

5.30%

发文量

2270

审稿时长

12 weeks

期刊介绍： The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.