Collagen fibril density modulates macrophage activation and cellular functions during tissue repair
Sapudom, Jiranuwat (New York University Abu Dhabi. Division of Engineering (United Arab Emirates))
Mohamed, Walaa Kamal E. (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Garcia Sabaté, Anna (New York University Abu Dhabi. Division of Engineering (United Arab Emirates))
Alatoom, Aseel (New York University Abu Dhabi. Division of Engineering (United Arab Emirates))
Karaman, Shaza (New York University Abu Dhabi. Division of Engineering (United Arab Emirates))
Mahtani, Nikhil (New York University Abu Dhabi. Division of Engineering (United Arab Emirates))
Teo, Jeremy C. M. (New York University. Department of Mechanical and Biomedical Engineering)

Date:	2020
Abstract:	Monocytes circulate in the bloodstream, extravasate into the tissue and differentiate into specific macrophage phenotypes to fulfill the immunological needs of tissues. During the tissue repair process, tissue density transits from loose to dense tissue. However, little is known on how changes in tissue density affects macrophage activation and their cellular functions. In this work, monocytic cell line THP-1 cells were embedded in three-dimensional (3D) collagen matrices with different fibril density and were then differentiated into uncommitted macrophages (M) using phorbol-12-myristate-13-acetate (PMA). M macrophages were subsequently activated into pro-inflammatory macrophages (M) and anti-inflammatory macrophages (M) using lipopolysaccharide and interferon-gamma (IFNγ), and interleukin 4 (IL-4) and IL-13, respectively. Although analysis of cell surface markers, on both gene and protein levels, was inconclusive, cytokine secretion profiles, however, demonstrated differences in macrophage phenotype. In the presence of differentiation activators, M secreted high amounts of IL-1β and tumor necrosis factor alpha (TNFα), while M0 secreted similar cytokines to M, but low IL-8. After removing the activators and further culture for 3 days in fresh cell culture media, the secretion of IL-6 was found in high concentrations by M, followed by M and M. Interestingly, the secretion of cytokines is enhanced with an increase of fibril density. Through the investigation of macrophage-associated functions during tissue repair, we demonstrated that M1 has the potential to enhance monocyte infiltration into tissue, while M supported fibroblast differentiation into myofibroblasts via transforming growth factor beta 1 (TGF-β1) in dependence of fibril density, suggesting a M2a-like phenotype. Overall, our results suggest that collagen fibril density can modulate macrophage response to favor tissue functions. Understanding of immune response in such complex 3D microenvironments will contribute to the novel therapeutic strategies for improving tissue repair, as well as guidance of the design of immune-modulated materials.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Macrophage ; Collagen fibril density ; Immunomechanobiology ; Monocyte infiltration ; Fibroblast differentiation
Published in:	Bioengineering, Vol. 7, Issue 2 (June 2020) , art. 33, ISSN 2306-5354

DOI: 10.3390/bioengineering7020033
PMID: 32244521

19 p, 7.7 MB

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