ORIGINAL RESEARCH article

Front. Bioeng. Biotechnol.

Sec. Biomaterials

Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1578467

Generation of Decellularized Human Brain Tissue for Investigating Cell-Matrix Interactions: A Proof-of-Concept Study

Provisionally accepted
Roemel Jeusep BuenoRoemel Jeusep Bueno1,2Camila Fernandez ZapataCamila Fernandez Zapata1Maren SallaMaren Salla3,4,5Juliana Campo GarciaJuliana Campo Garcia1Aylin AlacamAylin Alacam6Oliver KleinOliver Klein7Chotima BöttcherChotima Böttcher1Helena RadbruchHelena Radbruch8Friedemann PaulFriedemann Paul1Sarah C StarossomSarah C Starossom1Rafaela Vieira Da SilvaRafaela Vieira Da Silva1Carmen Infante-DuarteCarmen Infante-Duarte1*
  • 1Experimental and Clinical Research Center, Charite University Medicine Berlin, Berlin, Baden-Wurttemberg, Germany
  • 2Faculty of Life Sciences, Humboldt University of Berlin, Berlin, Berlin, Germany
  • 3The Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Helmholtz Association of German Research Centers (HZ), Berlin, Baden-Württemberg, Germany
  • 4Berlin Institute of Health, Charité Medical University of Berlin, Berlin, Baden-Württemberg, Germany
  • 5Department of Biology, Chemistry and Pharmacy, Free University of Berlin, Berlin, Berlin, Germany
  • 6Charité University Medicine Berlin, Berlin, Baden-Wurttemberg, Germany
  • 7Berlin-Brandenburg Center for Regenerative Therapies, Charité Medical University of Berlin, Berlin, Baden-Wurttemberg, Germany
  • 8Department of Neuropathology, Charité University Medicine Berlin, Berlin, Baden-Württemberg, Germany

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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 antiinflammatory 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.

Keywords: Brain extracellular matrix, Matrisome, Neuronal Stem Cells, Monocytes, Brain proteomics, imaging mass cytometry

Received: 17 Feb 2025; Accepted: 16 May 2025.

Copyright: © 2025 Bueno, Fernandez Zapata, Salla, Campo Garcia, Alacam, Klein, Böttcher, Radbruch, Paul, Starossom, Vieira Da Silva and Infante-Duarte. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Carmen Infante-Duarte, Experimental and Clinical Research Center, Charite University Medicine Berlin, Berlin, 13125, Baden-Wurttemberg, Germany

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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