Nanotopography reveals metabolites that maintain the immunosuppressive phenotype of mesenchymal stem cells

Ross, E.; Turner, L.-A.; Saeed, A.; Burgess, K.; Blackburn, G.; Reynolds, P.; Wells, J.; Mountford, J.; Gadegaard, N.; Salmeron-Sanchez, M.; Oreffo, R.; Dalby, M.

doi:10.1101/603332

bioRxiv · 10.1101/603332

Nanotopography reveals metabolites that maintain the immunosuppressive phenotype of mesenchymal stem cells

Ross, E.·Turner, L.-A.·Saeed, A.·Burgess, K.·Blackburn, G.·Reynolds, P.·Wells, J.·Mountford, J.·Gadegaard, N.·Salmeron-Sanchez, M.·Oreffo, R.·Dalby, M.

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Abstract

Mesenchymal stem cells (MSCs) are multipotent stem cells that are immunosuppressive and thus of considerable therapeutic potential in transplant operations. However, MSCs rapidly differentiate once in culture, making their large-scale expansion for use in immunosuppressive therapies challenging. Although the differentiation mechanisms of MSCs have been extensively investigated using materials, little is known about how materials can modulate paracrine activities of MSCs. Here, we show for the first time that nanotopography can control the immunomodulatory capacity of MSCs through decreased intracellular tension increasing oxidative glycolysis. We also use the nanotopography to identify bioactive metabolites that modulate intracellular tension, growth and immunomodulatory phenotype of MSCs in standard culture. Our findings show a novel route to support large-scale expansion of functional MSCs for therapeutic purposes

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Ross, E., Turner, L.-A., Saeed, A., Burgess, K., Blackburn, G., Reynolds, P., Wells, J., Mountford, J., Gadegaard, N., Salmeron-Sanchez, M., Oreffo, R., Dalby, M.. 2019-04-09. Nanotopography reveals metabolites that maintain the immunosuppressive phenotype of mesenchymal stem cells. https://doi.org/10.1101/603332

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