Modulating pro-fibrotic macrophages using yeast beta-glucan microparticles prepared by Pressurized Gas eXpanded liquid (PGX) Technology®.

Autor: Naiel S; Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, 50 Charlton Avenue East, L314-5, Hamilton, ON, L8N 4A6, Canada., Dowdall N; Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4L8, Canada., Zhou Q; Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4L8, Canada., Ali P; Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, 50 Charlton Avenue East, L314-5, Hamilton, ON, L8N 4A6, Canada., Hayat A; Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, 50 Charlton Avenue East, L314-5, Hamilton, ON, L8N 4A6, Canada., Vierhout M; Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, 50 Charlton Avenue East, L314-5, Hamilton, ON, L8N 4A6, Canada., Wong EY; Ceapro Inc., 7824 51 Ave NW, Edmonton, AB, T6E 6W2, Canada., Couto R; Ceapro Inc., 7824 51 Ave NW, Edmonton, AB, T6E 6W2, Canada., Yépez B; Ceapro Inc., 7824 51 Ave NW, Edmonton, AB, T6E 6W2, Canada., Seifried B; Ceapro Inc., 7824 51 Ave NW, Edmonton, AB, T6E 6W2, Canada., Moquin P; Ceapro Inc., 7824 51 Ave NW, Edmonton, AB, T6E 6W2, Canada., Kolb MR; Department of Pathology and Molecular Medicine, McMaster Immunology Research Center, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4L8, Canada., Ask K; Department of Medicine, Firestone Institute for Respiratory Health, McMaster University, 50 Charlton Avenue East, L314-5, Hamilton, ON, L8N 4A6, Canada. Electronic address: askkj@mcmaster.ca., Hoare T; Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4L8, Canada. Electronic address: hoaretr@mcmaster.ca.
Jazyk: angličtina
Zdroj: Biomaterials [Biomaterials] 2025 Feb; Vol. 313, pp. 122816. Date of Electronic Publication: 2024 Sep 05.
DOI: 10.1016/j.biomaterials.2024.122816
Abstrakt: Pro-fibrotic M2-like macrophages are widely implicated in the pathogenesis and progression of lung fibrosis due to their production of pro-fibrotic growth factors and cytokines. Yeast beta-glucan (YBG) microparticles have shown potential as immunomodulators that can convert macrophage polarization from a pro-fibrotic phenotype to an anti-fibrotic phenotype through the engagement of the Dectin-1 receptor. However, the processing conditions used to fabricate YBG microparticles can lead to unpredictable immunomodulatory effects. Herein, we report the use of Pressurized Gas eXpanded liquids (PGX) Technology® to fabricate YBG (PGX-YBG) microparticles with higher surface areas, lower densities, and smaller and more uniform size distributions compared to commercially available spray-dried YBGs. PGX-YBG is shown to activate Dectin-1 more efficiently in vitro while avoiding significant TLR 2/4 activation. Furthermore, PGX-YBG microparticles effectively modulate M2-like fibrosis-inducing murine and human macrophages into fibrosis-suppressing macrophages both in vitro as well as in ex vivo precision-cut murine lung slices, suggesting their potential utility as a therapeutic for addressing a broad spectrum of fibrotic end-point lung diseases.
Competing Interests: Declaration of competing interest This work has been conducted in collaboration with Ceapro Inc. (Edmonton, AB, Canada), which provided significant in-kind support to the research as well as a financial contribution to the Mitacs Canada grant. Ceapro Inc. is actively working to commercialize PGX-YBG for various applications which may include the treatment of fibrotic diseases. However, none of the academic authors hold any stake in the company nor would they benefit financially from any successful commercialization of the technology.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE