Human macrophage polarisation and regulation of angiogenesis and osteogenesis is dependent on culture extracellular matrix and dimensionality.

Autor: Petrousek SR; Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), Ireland; Department of Mechanical, Manufacturing, and Biomedical Engineering, School of Engineering, Trinity College Dublin, Ireland., Kronemberger GS; Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), Ireland; Department of Mechanical, Manufacturing, and Biomedical Engineering, School of Engineering, Trinity College Dublin, Ireland., O'Rourke SA; Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), Ireland; Department of Mechanical, Manufacturing, and Biomedical Engineering, School of Engineering, Trinity College Dublin, Ireland; School of Biochemistry & Immunology and School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland., Shanley LC; Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), Ireland; Department of Mechanical, Manufacturing, and Biomedical Engineering, School of Engineering, Trinity College Dublin, Ireland; School of Biochemistry & Immunology and School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland., Dunne A; Advanced Materials and Bioengineering Research Centre (AMBER), Ireland; School of Biochemistry & Immunology and School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland., Kelly DJ; Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), Ireland; Department of Mechanical, Manufacturing, and Biomedical Engineering, School of Engineering, Trinity College Dublin, Ireland., Hoey DA; Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), Ireland; Department of Mechanical, Manufacturing, and Biomedical Engineering, School of Engineering, Trinity College Dublin, Ireland. Electronic address: dahoey@tcd.ie.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Nov 26; Vol. 735, pp. 150835. Date of Electronic Publication: 2024 Oct 16.
DOI: 10.1016/j.bbrc.2024.150835
Abstrakt: The immune system plays a crucial role in tissue repair and regeneration. Macrophages have been identified as master regulators of the early immune response and healing outcome, by orchestrating the temporal nature of the initial inflammation phase and coordinating the fate of stem/progenitor cells involved in regeneration. However, traditional in-vitro models for the study of macrophages often fail to fully replicate the complexity of the in-vivo microenvironment, therefore generating models which do not fully capture the extensive spectrum of macrophage behaviour seen in native tissues. To this end, we used a hematoma-mimetic 3D fibrin matrix characteristic of early injured tissues to generate a 3D in-vitro model mirroring the local macrophage microenvironment. Leveraging this framework, we demonstrated significant effects of extracellular matrix and dimensionality on macrophage basal signalling and polarisation, achieving more pronounced regenerative phenotypes upon stimulation with the M2a polarisation factors compared to traditional 2D tissue culture conditions. Moreover, this enhanced physiological macrophage behaviour corresponded to increased coordination of angiogenesis and osteogenesis, better mirroring the healing processes seen in-vivo. Taken together, this study demonstrates the critical importance of integrating tissue composition and 3D architecture when investigating the macrophage behaviour in-vitro, establishing a powerful tool that overcomes known limitations associated with traditional 2D culture on plastic, and can be used to identify and validate novel immunomodulation strategies to enhance tissue regeneration.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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