Development of immunocompetent full thickness skin tissue constructs to model skin fibrosis for high-throughput drug screening.

Autor:	Lim YW; National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, United States of America., Quinn R; National Eye Institute, National Institutes of Health, Bethesda, MD 20814, United States of America., Bharti K; National Eye Institute, National Institutes of Health, Bethesda, MD 20814, United States of America., Ferrer M; National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, United States of America., Zarkoob H; National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, United States of America., Song MJ; National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, United States of America.
Jazyk:	angličtina
Zdroj:	Biofabrication [Biofabrication] 2024 Dec 13; Vol. 17 (1). Date of Electronic Publication: 2024 Dec 13.
DOI:	10.1088/1758-5090/ad998c
Abstrakt:	The lack of the immune component in most of the engineered skin models remains a challenge to study the interplay between different immune and non-immune cell types of the skin. Immunocompetent human in vitro skin models offer potential advantages in recapitulating in vivo like behavior which can serve to accelerate translational research and therapeutics development for skin diseases. Here we describe a three-dimensional human full-thickness skin (FTS) equivalent incorporating polarized M1 and M2 macrophages from human peripheral CD14 + monocytes. This macrophage-incorporated FTS model demonstrates discernible immune responses with physiologically relevant cytokine production and macrophage plasticity under homeostatic and lipopolysaccharide stimulation conditions. M2-incorporated FTS recapitulates skin fibrosis phenotypes with transforming growth factor- β 1 treatment as reflected by significant collagen deposition and myofibroblast expression, demonstrating a M2 potentiation effect. In conclusion, we successfully biofabricated an immunocompetent FTS with functional macrophages in a high-throughput (HT) amenable format. This model is the first step towards a HT-assay platform to develop new therapeutics for skin diseases. (Creative Commons Attribution license.)
Databáze:	MEDLINE
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