Nanotopography reveals metabolites that maintain the immunomodulatory phenotype of mesenchymal stromal cells


Mesenchymal stromal cells (MSCs) are multipotent progenitor cells that are of considerable clinical potential in transplantation and anti-inflammatory therapies due to their capacity for tissue repair and immunomodulation. However, MSCs rapidly differentiate once in culture, making their large-scale expansion for use in immunomodulatory therapies challenging. Although the differentiation mechanisms of MSCs have been extensively investigated using materials, little is known about how materials can influence paracrine activities of MSCs. Here, we show that nanotopography can control the immunomodulatory capacity of MSCs through decreased intracellular tension and increasing oxidative glycolysis. We use nanotopography to identify bioactive metabolites that modulate intracellular tension, growth and immunomodulatory phenotype of MSCs in standard culture and during larger scale cell manufacture. Our findings demonstrate an effective route to support large-scale expansion of functional MSCs for therapeutic purposes.

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Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Business and Social Sciences > Aston Business School > Economics, Finance & Entrepreneurship
Additional Information: Copyright © The Author(s), 2023. 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 Funding Information: This work was supported by BBSRC funded grants BB/N018419/1, BB/K011235/1 and BB/L021072/1.
Publication ISSN: 2041-1723
Last Modified: 18 Apr 2024 07:20
Date Deposited: 14 Feb 2023 10:23
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https://www.nat ... 467-023-36293-7 (Publisher URL)
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PURE Output Type: Article
Published Date: 2023-02-10
Accepted Date: 2023-01-25
Submitted Date: 2021-12-09
Authors: Ross, Ewan A. (ORCID Profile 0000-0001-5733-9361)
Turner, Lesley-Anne
Donnelly, Hannah
Saeed, Anwer
Tsimbouri, Monica P.
Burgess, Karl V.
Blackburn, Gavin
Jayawarna, Vineetha
Xiao, Yinbo
Oliva, Mariana A. G.
Willis, Jennifer
Bansal, Jaspreet
Reynolds, Paul (ORCID Profile 0000-0003-4383-8690)
Wells, Julia A.
Mountford, Joanne
Vassalli, Massimo
Gadegaard, Nikolaj
Oreffo, Richard O. C.
Salmeron-Sanchez, Manuel
Dalby, Matthew J.

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