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The cytokine secretion profile of mesenchymal stromal cells is determined by surface structure of the microenvironment

Mesenchymal stromal cells (MSC) secrete factors that contribute to organ homeostasis and repair in a tissue specific manner. For instance, kidney perivascular mesenchymal stromal cells (kPSCs) can facilitate renal epithelial repair through secretion of hepatocyte growth factor (HGF) while the secret...

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Autores principales: Leuning, Daniëlle G., Beijer, Nick R. M., du Fossé, Nadia A., Vermeulen, Steven, Lievers, Ellen, van Kooten, Cees, Rabelink, Ton J., Boer, Jan de
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956003/
https://www.ncbi.nlm.nih.gov/pubmed/29769543
http://dx.doi.org/10.1038/s41598-018-25700-5
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author Leuning, Daniëlle G.
Beijer, Nick R. M.
du Fossé, Nadia A.
Vermeulen, Steven
Lievers, Ellen
van Kooten, Cees
Rabelink, Ton J.
Boer, Jan de
author_facet Leuning, Daniëlle G.
Beijer, Nick R. M.
du Fossé, Nadia A.
Vermeulen, Steven
Lievers, Ellen
van Kooten, Cees
Rabelink, Ton J.
Boer, Jan de
author_sort Leuning, Daniëlle G.
collection PubMed
description Mesenchymal stromal cells (MSC) secrete factors that contribute to organ homeostasis and repair in a tissue specific manner. For instance, kidney perivascular mesenchymal stromal cells (kPSCs) can facilitate renal epithelial repair through secretion of hepatocyte growth factor (HGF) while the secretome of bone marrow MSCs gives rise to immunosuppression. Stromal cells function in a complex 3-dimensional (3D) connective tissue architecture that induces conformational adaptation. Here we tested the hypothesis that surface topography and associated cell adaptations dictate stromal cell function through tuning of the cytokines released. To this end, we cultured human bone marrow and kidney perivascular stromal cells in the TopoWell plate, a custom-fabricated multi-well plate containing 76 unique bioactive surface topographies. Using fluorescent imaging, we observed profound changes in cell shape, accompanied by major quantitative changes in the secretory capacity of the MSCs. The cytokine secretion profile was closely related to cell morphology and was stromal cell type specific. Our data demonstrate that stromal cell function is determined by microenvironment structure and can be manipulated in an engineered setting. Our data also have implications for the clinical manufacturing of mesenchymal stromal cell therapy, where surface topography during bioreactor expansion should be taken into account to preserve therapeutic properties.
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spelling pubmed-59560032018-05-21 The cytokine secretion profile of mesenchymal stromal cells is determined by surface structure of the microenvironment Leuning, Daniëlle G. Beijer, Nick R. M. du Fossé, Nadia A. Vermeulen, Steven Lievers, Ellen van Kooten, Cees Rabelink, Ton J. Boer, Jan de Sci Rep Article Mesenchymal stromal cells (MSC) secrete factors that contribute to organ homeostasis and repair in a tissue specific manner. For instance, kidney perivascular mesenchymal stromal cells (kPSCs) can facilitate renal epithelial repair through secretion of hepatocyte growth factor (HGF) while the secretome of bone marrow MSCs gives rise to immunosuppression. Stromal cells function in a complex 3-dimensional (3D) connective tissue architecture that induces conformational adaptation. Here we tested the hypothesis that surface topography and associated cell adaptations dictate stromal cell function through tuning of the cytokines released. To this end, we cultured human bone marrow and kidney perivascular stromal cells in the TopoWell plate, a custom-fabricated multi-well plate containing 76 unique bioactive surface topographies. Using fluorescent imaging, we observed profound changes in cell shape, accompanied by major quantitative changes in the secretory capacity of the MSCs. The cytokine secretion profile was closely related to cell morphology and was stromal cell type specific. Our data demonstrate that stromal cell function is determined by microenvironment structure and can be manipulated in an engineered setting. Our data also have implications for the clinical manufacturing of mesenchymal stromal cell therapy, where surface topography during bioreactor expansion should be taken into account to preserve therapeutic properties. Nature Publishing Group UK 2018-05-16 /pmc/articles/PMC5956003/ /pubmed/29769543 http://dx.doi.org/10.1038/s41598-018-25700-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Leuning, Daniëlle G.
Beijer, Nick R. M.
du Fossé, Nadia A.
Vermeulen, Steven
Lievers, Ellen
van Kooten, Cees
Rabelink, Ton J.
Boer, Jan de
The cytokine secretion profile of mesenchymal stromal cells is determined by surface structure of the microenvironment
title The cytokine secretion profile of mesenchymal stromal cells is determined by surface structure of the microenvironment
title_full The cytokine secretion profile of mesenchymal stromal cells is determined by surface structure of the microenvironment
title_fullStr The cytokine secretion profile of mesenchymal stromal cells is determined by surface structure of the microenvironment
title_full_unstemmed The cytokine secretion profile of mesenchymal stromal cells is determined by surface structure of the microenvironment
title_short The cytokine secretion profile of mesenchymal stromal cells is determined by surface structure of the microenvironment
title_sort cytokine secretion profile of mesenchymal stromal cells is determined by surface structure of the microenvironment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956003/
https://www.ncbi.nlm.nih.gov/pubmed/29769543
http://dx.doi.org/10.1038/s41598-018-25700-5
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