Fibronectin/thermo-responsive polymer scaffold as a dynamic ex vivo niche for mesenchymal stem cells
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TISSUE ENGINEERING CONSTRUCTS AND CELL SUBSTRATES Original Research
Fibronectin/thermo-responsive polymer scaffold as a dynamic ex vivo niche for mesenchymal stem cells Laura Ramalho1,2 Salima Nedjari1 Roberto Guarino George Altankov1,4,7 ●
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Firas Awaja4,5,6 Dencho Gugutkov1 ●
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Received: 20 January 2020 / Accepted: 31 October 2020 / Published online: 30 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract In this paper, we created a dynamic adhesive environment (DAE) for adipose tissue-derived mesenchymal stem cells (ADMSCs) cultured on smart thermo-responsive substrates, i.e., poly (N-isopropyl acrylamide) (PNIPAM), via introducing periodic changes in the culture temperature. We further explored the particular role of adsorbed fibronectin (FN), an important cell adhesive protein that was recently attributed to the recruitment of stem cells in the niche. The engineered FN/ PNIPAM DAE system significantly increased the symmetric renewal of ADMSCs, particularly between passages 7 and 9 (p7–p9), before it dropped down to the level of the control (FN-coated TC polystyrene). This decline in the growth curve was consistent with the increased number of senescent cells, the augmented average cell size and the suppressed FN matrix secretion at late passages (p10–p12), all of them characteristic for stem cells ageing, which equivocally tended to slow down at our DAE system. FN supported also the osteogenic response of ADMSCs (apart from the previous observations with plain PNIPAM substrata) indicated by the significant increase of alkaline phosphatase (ALP) activity at days 7 and 14. The minimal changes in the Ca deposition, however, suggest a restricted effect of DAE on the early osteogenic response of ADMSCs only. Thus, the engineering of niche-like DAE involving FN uncovers a new tissue engineering strategy for gaining larger amounts of functionally active stem cells for clinical application. Graphical Abstract
* George Altankov [email protected]
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Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain
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Engmat Ltd., Clybaun Road, Galway, Ireland
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ICREA, Barcelona, Spain
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Institute of Biophysics and Biomedical Engineering, Faculty of Sciences, University of Lisbon, Lisbon, Portugal
Present address: Regenerative Medicine Institute (REMEDI) and Centre for Research in Medical Devices (CÚRAM) at National University of Ireland, Galway, Ireland
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École Polytechnique Fédérale de Lausanne (EPFL), Swiss Plasma Center (SPC), CH-5232 Villigen PSI, Switzerland
Present address: Associate Member Institute for Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Sofia, Bulgaria
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1 Introduction Adult stem cells (ASCs) are major contributors for the growth and regeneration of tissues after damage or ageing [1–5]. They have great therapeutic potential due to the unique ability to differentiate into multiple cell lineages, thus assuring diverse tissue repair [3, 6]. However, most cellbased the
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