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

Ross, E. A. et al. (2023) Nanotopography reveals metabolites that maintain the immunomodulatory phenotype of mesenchymal stromal cells. Nature Communications, 14, 753. (doi: 10.1038/s41467-023-36293-7) (PMID:36765065) (PMCID:PMC9918539)

Abstract

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.

• Item Type: Articles
• Additional Information: This work was supported by BBSRC funded grants BB/N018419/1, BB/K011235/1 and BB/L021072/1.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Saeed, Dr Anwer and Blackburn, Dr Gavin and Tsimbouri, Dr Monica and Vassalli, Professor Massimo and Mountford, Dr Joanne and Reynolds, Dr Paul and Xiao, Yinbo and Burgess, Dr Karl and Salmeron-Sanchez, Professor Manuel and Jayawarna, Dr Vineetha and Ross, Dr Ewan and Gadegaard, Professor Nikolaj and Donnelly, Dr Hannah and Dalby, Professor Matthew and Turner, Dr Lesley-Anne and Willis, Jennifer
• Authors: Ross, E. A., Turner, L.-A., Donnelly, H., Saeed, A., Tsimbouri, M., Burgess, K. V., Blackburn, G., Jayawarna, V., Xiao, Y., Oliva, M. A.G., Willis, J., Bansal, J., Reynolds, P., Wells, J. A., Mountford, J., Vassalli, M., Gadegaard, N., Oreffo, R. O.C., Salmeron-Sanchez, M., and Dalby, M. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Molecular Biosciences; College of Science and Engineering > School of Chemistry; College of Science and Engineering > School of Engineering > Biomedical Engineering; College of Science and Engineering > School of Engineering > James Watt Nanofabrication Centre
• Research Centre: Mazumdar-Shaw Advanced Research Centre (ARC) > Technologies Touching Life
• Journal Name: Nature Communications
• Publisher: Nature Research
• ISSN: 2041-1723
• ISSN (Online): 2041-1723
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Nature Communications 14: 753
• Publisher Policy: Reproduced under a Creative Commons License
• Data DOI: 10.5525/gla.researchdata.973

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172752		Materials exploitation of the biointerface to control MSC quality and niche phenotype	Matthew Dalby	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/N018419/1	Institute of Molecular, Cell & Systems Biology
190602		Development of nanopatterned substrates for the delivery of high quality stem cells	Nikolaj Gadegaard	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/K011235/1	ENG - Biomedical Engineering