title: Joint mimicking mechanical load activates TGFβ1 in fibrin-poly(ester-urethane) scaffolds seeded with mesenchymal stem cells.
abstract: Transforming growth factor-β1 (TGF-β1) is widely used in an active recombinant form to stimulate the chondrogenic differentiation of mesenchymal stem cells (MSCs). Recently, it has been shown that the application of multiaxial load, that mimics the loading within diarthrodial joints, to MSCs seeded in to fibrin-poly(ester-urethane) scaffolds leads to the endogenous production and secretion of TGF-β1 by the mechanically stimulated cells, which in turn drives the chondrogenic differentiation of the cells within the scaffold. The work presented in this short communication provides further evidence that the application of joint mimicking multiaxial load induces the secretion of TGF-β1 by mechanically stimulated MSCs. The results of this work also show that joint-like multiaxial mechanical load activates latent TGF-β1 in response to loading in the presence or absence of cells; this activation was not seen in non-loaded control scaffolds. Despite the application of mechanical load to scaffolds with different distributions/numbers of cells no significant differences were seen in the percentage of active TGF-β1 quantified in the culture medium of scaffolds from different groups. The similar level of activation in scaffolds containing different numbers of cells, cells at different stages of differentiation or with different distributions of cells suggests that this activation results from the mechanical forces applied to the culture system rather than differences in cellular behaviour. These results are relevant when considering rehabilitation protocols after cell therapy or microfracture, for articular cartilage repair, where increased TGF-β1 activation in response to joint mobilization may improve the quality of developing cartilaginous repair material. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: AO Research Institute Davos, Davos Platz, Switzerland.|School of Biosciences, Cardiff University, UK.
authors.forename: Oliver F W
authors.initials: OFW
authors.lastname: Gardner
authors.affiliation: AO Research Institute Davos, Davos Platz, Switzerland.
authors.forename: Niamh
authors.initials: N
authors.lastname: Fahy
authors.affiliation: AO Research Institute Davos, Davos Platz, Switzerland.
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.affiliation: AO Research Institute Davos, Davos Platz, Switzerland.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Stoddart
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D005337:Fibrin / Q000737:chemistry*; D006801:Humans; D007596:Joints; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D011091:Polyesters / Q000737:chemistry*; D011140:Polyurethanes / Q000737:chemistry*; D013314:Stress, Mechanical; D054457:Tissue Scaffolds / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D011091:Polyesters; D011140:Polyurethanes; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C081821:microthane foam; D005337:Fibrin
keywords: cartilage; endogenous TGF; growth factor; mechanobiology; paracrine; regeneration