Cell-controlled dynamic surfaces for skeletal stem cell growth and differentiation.

Autor: Anderson HJ; Centre for the Cellular Microenvironment, Institute of Molecular, Cell & Systems Biology, MVLS, University of Glasgow, Joseph Black Building, Glasgow, G12 8QQ, UK., Sahoo JK; Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, Glasgow, G1 1RD, UK.; Department of Biomedical Engineering, Science and Technology Centre, Tufts University, 4 Colby St., Medford, MA, 02155, USA., Wells J; Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK., van Nuffel S; School of Pharmacy, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, NG7 2RD, UK.; M4I, Faculty of Science and Engineering, Maastricht University, Maastricht, The Netherlands., Dhowre HS; School of Pharmacy, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, NG7 2RD, UK.; Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, 94305, USA., Oreffo ROC; Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton, SO16 6YD, UK., Zelzer M; School of Pharmacy, Biodiscovery Institute, University Park, University of Nottingham, Nottingham, NG7 2RD, UK., Ulijn RV; Nanoscience Initiative at Advanced Science Research Center (ASRC) of the Graduate Center of the City University of New York, New York, USA.; Department of Chemistry Hunter College, City University of New York, New York, USA.; Ph.D. Programs in Biochemistry and Chemistry, The Graduate Center of the City University of New York, New York, USA., Dalby MJ; Centre for the Cellular Microenvironment, Institute of Molecular, Cell & Systems Biology, MVLS, University of Glasgow, Joseph Black Building, Glasgow, G12 8QQ, UK. matthew.dalby@glasgow.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 May 17; Vol. 12 (1), pp. 8165. Date of Electronic Publication: 2022 May 17.
DOI: 10.1038/s41598-022-12057-z
Abstrakt: Skeletal stem cells (SSCs, or mesenchymal stromal cells typically referred to as mesenchymal stem cells from the bone marrow) are a dynamic progenitor population that can enter quiescence, self-renew or differentiate depending on regenerative demand and cues from their niche environment. However, ex vivo, in culture, they are grown typically on hard polystyrene surfaces, and this leads to rapid loss of the SSC phenotype. While materials are being developed that can control SSC growth and differentiation, very few examples of dynamic interfaces that reflect the plastic nature of the stem cells have, to date, been developed. Achieving such interfaces is challenging because of competing needs: growing SSCs require lower cell adhesion and intracellular tension while differentiation to, for example, bone-forming osteoblasts requires increased adhesion and intracellular tension. We previously reported a dynamic interface where the cell adhesion tripeptide arginine-glycine-aspartic acid (RGD) was presented to the cells upon activation by user-added elastase that cleaved a bulky blocking group hiding RGD from the cells. This allowed for a growth phase while the blocking group was in place and the cells could only form smaller adhesions, followed by an osteoblast differentiation phase that was induced after elastase was added which triggered exposure of RGD and subsequent cell adhesion and contraction. Here, we aimed to develop an autonomous system where the surface is activated according to the need of the cell by using matrix metalloprotease (MMP) cleavable peptide sequences to remove the blocking group with the hypothesis that the SSCs would produce higher levels of MMP as the cells reached confluence. The current studies demonstrate that SSCs produce active MMP-2 that can cleave functional groups on a surface. We also demonstrate that SSCs can grow on the uncleaved surface and, with time, produce osteogenic marker proteins on the MMP-responsive surface. These studies demonstrate the concept for cell-controlled surfaces that can modulate adhesion and phenotype with significant implications for stem cell phenotype modulation.
(© 2022. The Author(s).)
Databáze: MEDLINE
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