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; Matthew J. Dalby

doi:10.1038/s41467-023-36293-7

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
, Matthew J. Dalby^*

^*Corresponding author for this work

University of Glasgow, Centre for the Cellular Microenvironment, School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, Mazumdar-Shaw Advanced Research Centre, Glasgow, G11 6EW, UK, GRID: grid.8756.c, ISNI: 0000 0001 2193 314X
University of Glasgow, Division of Biomedical Engineering, James Watt School of Engineering, Glasgow, G12 8QQ, UK, GRID: grid.8756.c, ISNI: 0000 0001 2193 314X
Garscube Campus, Bearsden, Glasgow Polyomics, Wolfson Wohl Cancer Research Centre, Glasgow, G61 1QH, UK, GRID: grid.8756.c, ISNI: 0000 0001 2193 314X
University of Glasgow, Centre for the Cellular Microenvironment, Division of Biomedical Engineering, James Watt School of Engineering, Mazumdar-Shaw Advanced Research Centre, Glasgow, G11 6EW, UK, GRID: grid.8756.c, ISNI: 0000 0001 2193 314X
University of Southampton, Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, Southampton, SO16 6YD, UK, GRID: grid.5491.9, ISNI: 0000 0004 1936 9297
Jack Copland Centre, Scottish National Blood Transfusion Service, Advanced Therapeutics, 52 Research Avenue North, Heriot Watt Research Park, Edinburgh, EH14 4BE, UK, GRID: grid.476695.f, ISNI: 0000 0004 0495 4557

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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.

Original language	English
Article number	753
Number of pages	16
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-36293-7
Publication status	Published - 10 Feb 2023

Bibliographical note

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 https://creativecommons.org/licenses/by/4.0/

Funding Information: This work was supported by BBSRC funded grants BB/N018419/1, BB/K011235/1 and BB/L021072/1.

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10.1038/s41467-023-36293-7Licence: CC BY 4.0

E A Ross et al_Nanotopography metabolites that maintain immunomodulatory phenotype mesenchumal stem cells
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 https://creativecommons.org/licenses/by/4.0/.
Final published version, 2.46 MBLicence: CC BY 4.0
Supplementary Information 41467_2023_36293_MOESM1_ESM.pdf
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 http://creativecommons.org/licenses/by/4.0/.
Other version, 1.38 MBLicence: CC BY 4.0

Cite this

Ross, E. A., Turner, L.-A., Donnelly, H., Saeed, A., Tsimbouri, M. P., 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., & Dalby, M. J. (2023). Nanotopography reveals metabolites that maintain the immunomodulatory phenotype of mesenchymal stromal cells. Nature Communications, 14(1), Article 753. https://doi.org/10.1038/s41467-023-36293-7

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title = "Nanotopography reveals metabolites that maintain the immunomodulatory phenotype of mesenchymal stromal cells",

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.",

author = "Ross, \{Ewan A.\} and Lesley-Anne Turner and Hannah Donnelly and Anwer Saeed and Tsimbouri, \{Monica P.\} and Burgess, \{Karl V.\} and Gavin Blackburn and Vineetha Jayawarna and Yinbo Xiao and Oliva, \{Mariana A. G.\} and Jennifer Willis and Jaspreet Bansal and Paul Reynolds and Wells, \{Julia A.\} and Joanne Mountford and Massimo Vassalli and Nikolaj Gadegaard and Oreffo, \{Richard O. C.\} and Manuel Salmeron-Sanchez and Dalby, \{Matthew J.\}",

note = "Copyright {\textcopyright} 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{\textquoteright}s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article{\textquoteright}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 https://creativecommons.org/licenses/by/4.0/ Funding Information: This work was supported by BBSRC funded grants BB/N018419/1, BB/K011235/1 and BB/L021072/1.",

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doi = "10.1038/s41467-023-36293-7",

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Ross, EA, Turner, L-A, Donnelly, H, Saeed, A, Tsimbouri, MP, Burgess, KV, Blackburn, G, Jayawarna, V, Xiao, Y, Oliva, MAG, Willis, J, Bansal, J, Reynolds, P, Wells, JA, Mountford, J, Vassalli, M, Gadegaard, N, Oreffo, ROC, Salmeron-Sanchez, M & Dalby, MJ 2023, 'Nanotopography reveals metabolites that maintain the immunomodulatory phenotype of mesenchymal stromal cells', Nature Communications, vol. 14, no. 1, 753. https://doi.org/10.1038/s41467-023-36293-7

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AU - Ross, Ewan A.

AU - Turner, Lesley-Anne

AU - Donnelly, Hannah

AU - Saeed, Anwer

AU - Tsimbouri, Monica P.

AU - Burgess, Karl V.

AU - Blackburn, Gavin

AU - Jayawarna, Vineetha

AU - Xiao, Yinbo

AU - Oliva, Mariana A. G.

AU - Willis, Jennifer

AU - Bansal, Jaspreet

AU - Reynolds, Paul

AU - Wells, Julia A.

AU - Mountford, Joanne

AU - Vassalli, Massimo

AU - Gadegaard, Nikolaj

AU - Oreffo, Richard O. C.

AU - Salmeron-Sanchez, Manuel

AU - Dalby, Matthew J.

N1 - 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 https://creativecommons.org/licenses/by/4.0/ Funding Information: This work was supported by BBSRC funded grants BB/N018419/1, BB/K011235/1 and BB/L021072/1.

PY - 2023/2/10

Y1 - 2023/2/10

N2 - 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.

AB - 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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VL - 14

JO - Nature Communications

JF - Nature Communications

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

Abstract

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