Identification of extracellular matrix proteins secreted by human dermal fibroblasts cultured in 3D electrospun scaffolds

Abstract The appreciation that cell interactions in tissues is dependent on their three dimensional (3D) distribution has stimulated the development of 3D cell culture models. We constructed an artificial 3D tumour by culturing human breast cancer JIMT-1 cells and human dermal fibroblasts (HDFs) in...

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Autores principales: Atena Malakpour-Permlid, Irina Buzzi, Cecilia Hegardt, Fredrik Johansson, Stina Oredsson
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Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/88151e5832c749809f828ff0ec29c938
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spelling oai:doaj.org-article:88151e5832c749809f828ff0ec29c9382021-12-02T11:45:03ZIdentification of extracellular matrix proteins secreted by human dermal fibroblasts cultured in 3D electrospun scaffolds10.1038/s41598-021-85742-02045-2322https://doaj.org/article/88151e5832c749809f828ff0ec29c9382021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85742-0https://doaj.org/toc/2045-2322Abstract The appreciation that cell interactions in tissues is dependent on their three dimensional (3D) distribution has stimulated the development of 3D cell culture models. We constructed an artificial 3D tumour by culturing human breast cancer JIMT-1 cells and human dermal fibroblasts (HDFs) in a 3D network of electrospun polycaprolactone fibres. Here, we investigate ECM components produced by the cells in the artificial 3D tumour, which is an important step in validating the model. Immunostaining and confocal fluorescence microscopy show that the ECM proteins fibronectin, collagen I, and laminin are deposited throughout the entire 3D structure. Secreted soluble factors including matrix metalloproteinases (MMPs) and interleukine-6 (IL-6) were analysed in collected medium and were found to be mainly derived from the HDFs. Treatment with transforming growth factor-β1 (TGF-β1), a major cytokine found in a tumour, significantly alters the MMP activity and IL-6 concentration. In addition, TGF-β1 treatment, changes the morphology of the HDFs to become more elongated and with increased linearized actin filaments compared to non-treated HDFs. Collectively, these novel findings suggest that the artificial 3D tumour displays a clear cell distribution and ECM deposition that resembles a tumour environment in vivo, suggesting an innovative biological model to study a human tumour.Atena Malakpour-PermlidIrina BuzziCecilia HegardtFredrik JohanssonStina OredssonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Atena Malakpour-Permlid
Irina Buzzi
Cecilia Hegardt
Fredrik Johansson
Stina Oredsson
Identification of extracellular matrix proteins secreted by human dermal fibroblasts cultured in 3D electrospun scaffolds
description Abstract The appreciation that cell interactions in tissues is dependent on their three dimensional (3D) distribution has stimulated the development of 3D cell culture models. We constructed an artificial 3D tumour by culturing human breast cancer JIMT-1 cells and human dermal fibroblasts (HDFs) in a 3D network of electrospun polycaprolactone fibres. Here, we investigate ECM components produced by the cells in the artificial 3D tumour, which is an important step in validating the model. Immunostaining and confocal fluorescence microscopy show that the ECM proteins fibronectin, collagen I, and laminin are deposited throughout the entire 3D structure. Secreted soluble factors including matrix metalloproteinases (MMPs) and interleukine-6 (IL-6) were analysed in collected medium and were found to be mainly derived from the HDFs. Treatment with transforming growth factor-β1 (TGF-β1), a major cytokine found in a tumour, significantly alters the MMP activity and IL-6 concentration. In addition, TGF-β1 treatment, changes the morphology of the HDFs to become more elongated and with increased linearized actin filaments compared to non-treated HDFs. Collectively, these novel findings suggest that the artificial 3D tumour displays a clear cell distribution and ECM deposition that resembles a tumour environment in vivo, suggesting an innovative biological model to study a human tumour.
format article
author Atena Malakpour-Permlid
Irina Buzzi
Cecilia Hegardt
Fredrik Johansson
Stina Oredsson
author_facet Atena Malakpour-Permlid
Irina Buzzi
Cecilia Hegardt
Fredrik Johansson
Stina Oredsson
author_sort Atena Malakpour-Permlid
title Identification of extracellular matrix proteins secreted by human dermal fibroblasts cultured in 3D electrospun scaffolds
title_short Identification of extracellular matrix proteins secreted by human dermal fibroblasts cultured in 3D electrospun scaffolds
title_full Identification of extracellular matrix proteins secreted by human dermal fibroblasts cultured in 3D electrospun scaffolds
title_fullStr Identification of extracellular matrix proteins secreted by human dermal fibroblasts cultured in 3D electrospun scaffolds
title_full_unstemmed Identification of extracellular matrix proteins secreted by human dermal fibroblasts cultured in 3D electrospun scaffolds
title_sort identification of extracellular matrix proteins secreted by human dermal fibroblasts cultured in 3d electrospun scaffolds
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/88151e5832c749809f828ff0ec29c938
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