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

Ewan A. Ross, Lesley-Anne Turner, Hannah Donnelly, Anwer Saeed, Monica P. Tsimbouri, Karl V. Burgess, Gavin Blackburn, Vineetha Jayawarna, Yinbo Xiao, Mariana A. G. Oliva, Jennifer Willis, Jaspreet Bansal, Paul Reynolds, Julia A. Wells, Joanne Mountford, Massimo Vassalli, Nikolaj Gadegaard, Richard O. C. Oreffo, Manuel Salmeron-Sanchez and Matthew J. Dalby ()
Additional contact information
Ewan A. Ross: University of Glasgow
Lesley-Anne Turner: University of Glasgow
Hannah Donnelly: University of Glasgow
Anwer Saeed: University of Glasgow
Monica P. Tsimbouri: University of Glasgow
Karl V. Burgess: Garscube Campus, Bearsden
Gavin Blackburn: Garscube Campus, Bearsden
Vineetha Jayawarna: University of Glasgow
Yinbo Xiao: University of Glasgow
Mariana A. G. Oliva: University of Glasgow
Jennifer Willis: Aston University
Jaspreet Bansal: Aston University
Paul Reynolds: University of Glasgow
Julia A. Wells: University of Southampton
Joanne Mountford: Jack Copland Centre
Massimo Vassalli: University of Glasgow
Nikolaj Gadegaard: University of Glasgow
Richard O. C. Oreffo: University of Southampton
Manuel Salmeron-Sanchez: University of Glasgow
Matthew J. Dalby: University of Glasgow

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36293-7

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DOI: 10.1038/s41467-023-36293-7

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