Nanotopography reveals metabolites that maintain the immunomodulatory phenotype of mesenchymal stromal cells
Ewan A. Ross, Lesley-Anne Turner, Hannah Donnelly, Anwer Saeed, Penelope M. Tsimbouri, Karl Burgess, Gavin Blackburn, Vineetha Jayawarna, Yinbo Xiao, Mariana Azevedo González Oliva, Jennifer Willis, Jaspreet Bansal, P. Reynolds, Julia Wells, Joanne C. Mountford, Massimo Vassalli, Nikolaj Gadegaard, Richard O. C. Oreffo, Manuel Salmerón‐Sánchez, Matthew J. Dalby
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.