3D in vitro M2 macrophage model to mimic modulation of tissue repair

Abstract Distinct anti-inflammatory macrophage (M2) subtypes, namely M2a and M2c, are reported to modulate the tissue repair process tightly and chronologically by modulating fibroblast differentiation state and functions. To establish a well-defined three-dimensional (3D) cell culture model to mimi...

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Autores principales: Jiranuwat Sapudom, Shaza Karaman, Walaa K. E. Mohamed, Anna Garcia-Sabaté, Brian C. Quartey, Jeremy C. M. Teo
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/df8378eacbdc424884f4426f5edffb1e
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spelling oai:doaj.org-article:df8378eacbdc424884f4426f5edffb1e2021-12-05T12:24:36Z3D in vitro M2 macrophage model to mimic modulation of tissue repair10.1038/s41536-021-00193-52057-3995https://doaj.org/article/df8378eacbdc424884f4426f5edffb1e2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41536-021-00193-5https://doaj.org/toc/2057-3995Abstract Distinct anti-inflammatory macrophage (M2) subtypes, namely M2a and M2c, are reported to modulate the tissue repair process tightly and chronologically by modulating fibroblast differentiation state and functions. To establish a well-defined three-dimensional (3D) cell culture model to mimic the tissue repair process, we utilized THP-1 human monocytic cells and a 3D collagen matrix as a biomimetic tissue model. THP-1 cells were differentiated into macrophages, and activated using IL-4/IL-13 (MIL-4/IL-13) and IL-10 (MIL-10). Both activated macrophages were characterized by both their cell surface marker expression and cytokine secretion profile. Our cell characterization suggested that MIL-4/IL-13 and MIL-10 demonstrate M2a- and M2c-like subtypes, respectively. To mimic the initial and resolution phases during the tissue repair, both activated macrophages were co-cultured with fibroblasts and myofibroblasts. We showed that MIL-4/IL-13 were able to promote matrix synthesis and remodeling by induction of myofibroblast differentiation via transforming growth factor beta-1 (TGF-β1). On the contrary, MIL-10 demonstrated the ability to resolve the tissue repair process by dedifferentiation of myofibroblast via IL-10 secretion. Overall, our study demonstrated the importance and the exact roles of M2a and M2c-like macrophage subtypes in coordinating tissue repair in a biomimetic model. The established model can be applied for high-throughput platforms for improving tissue healing and anti-fibrotic drugs testing, as well as other biomedical studies.Jiranuwat SapudomShaza KaramanWalaa K. E. MohamedAnna Garcia-SabatéBrian C. QuarteyJeremy C. M. TeoNature PortfolioarticleMedicineRENnpj Regenerative Medicine, Vol 6, Iss 1, Pp 1-13 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
spellingShingle Medicine
R
Jiranuwat Sapudom
Shaza Karaman
Walaa K. E. Mohamed
Anna Garcia-Sabaté
Brian C. Quartey
Jeremy C. M. Teo
3D in vitro M2 macrophage model to mimic modulation of tissue repair
description Abstract Distinct anti-inflammatory macrophage (M2) subtypes, namely M2a and M2c, are reported to modulate the tissue repair process tightly and chronologically by modulating fibroblast differentiation state and functions. To establish a well-defined three-dimensional (3D) cell culture model to mimic the tissue repair process, we utilized THP-1 human monocytic cells and a 3D collagen matrix as a biomimetic tissue model. THP-1 cells were differentiated into macrophages, and activated using IL-4/IL-13 (MIL-4/IL-13) and IL-10 (MIL-10). Both activated macrophages were characterized by both their cell surface marker expression and cytokine secretion profile. Our cell characterization suggested that MIL-4/IL-13 and MIL-10 demonstrate M2a- and M2c-like subtypes, respectively. To mimic the initial and resolution phases during the tissue repair, both activated macrophages were co-cultured with fibroblasts and myofibroblasts. We showed that MIL-4/IL-13 were able to promote matrix synthesis and remodeling by induction of myofibroblast differentiation via transforming growth factor beta-1 (TGF-β1). On the contrary, MIL-10 demonstrated the ability to resolve the tissue repair process by dedifferentiation of myofibroblast via IL-10 secretion. Overall, our study demonstrated the importance and the exact roles of M2a and M2c-like macrophage subtypes in coordinating tissue repair in a biomimetic model. The established model can be applied for high-throughput platforms for improving tissue healing and anti-fibrotic drugs testing, as well as other biomedical studies.
format article
author Jiranuwat Sapudom
Shaza Karaman
Walaa K. E. Mohamed
Anna Garcia-Sabaté
Brian C. Quartey
Jeremy C. M. Teo
author_facet Jiranuwat Sapudom
Shaza Karaman
Walaa K. E. Mohamed
Anna Garcia-Sabaté
Brian C. Quartey
Jeremy C. M. Teo
author_sort Jiranuwat Sapudom
title 3D in vitro M2 macrophage model to mimic modulation of tissue repair
title_short 3D in vitro M2 macrophage model to mimic modulation of tissue repair
title_full 3D in vitro M2 macrophage model to mimic modulation of tissue repair
title_fullStr 3D in vitro M2 macrophage model to mimic modulation of tissue repair
title_full_unstemmed 3D in vitro M2 macrophage model to mimic modulation of tissue repair
title_sort 3d in vitro m2 macrophage model to mimic modulation of tissue repair
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/df8378eacbdc424884f4426f5edffb1e
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