title: Induction of Tenogenic Differentiation Mediated by Extracellular Tendon Matrix and Short-Term Cyclic Stretching.
abstract: Tendon and ligament pathologies are still a therapeutic challenge, due to the difficulty in restoring the complex extracellular matrix architecture and biomechanical strength. While progress is being made in cell-based therapies and tissue engineering approaches, comprehensive understanding of the fate of progenitor cells in tendon healing is still lacking. The aim of this study was to investigate the effect of decellularized tendon matrix and moderate cyclic stretching as natural stimuli which could potentially direct tenogenic fate. Equine adipose-derived mesenchymal stromal cells (MSC) were seeded on decellularized tendon matrix scaffolds. Mechanical stimulation was applied in a custom-made cyclic strain bioreactor. Assessment was performed 4 h, 8 h, and 24 h following mechanical stimulation. Scaffold culture induced cell alignment and changes in expression of tendon-related genes, although cell viability was decreased compared to monolayer culture. Short mechanical stimulation periods enhanced most of the scaffold-induced effects. Collagen 1A2 expression levels were decreased, while collagen 3A1 and decorin levels were increased. Tenascin-C and scleraxis expression showed an initial decrease but had increased 24 h after stimulation. The results obtained suggest that decellularized tendon matrix, supported by cyclic stretching, can induce tenogenic differentiation and the synthesis of tendon components important for matrix remodeling.
authors.affiliation: Translational Centre for Regenerative Medicine, University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103 Leipzig, Germany; Saxon Incubator for Clinical Translation, University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103 Leipzig, Germany; Institute of Veterinary Physiology, University of Leipzig, An den Tierkliniken 7, 04103 Leipzig, Germany.
authors.forename: Janina
authors.identifier: 0000-0002-7868-0355
authors.initials: J
authors.lastname: Burk
authors.affiliation: Large Animal Clinic for Surgery, University of Leipzig, An den Tierkliniken 21, 04103 Leipzig, Germany.
authors.forename: Amelie
authors.initials: A
authors.lastname: Plenge
authors.affiliation: Translational Centre for Regenerative Medicine, University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103 Leipzig, Germany; Saxon Incubator for Clinical Translation, University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103 Leipzig, Germany; Large Animal Clinic for Surgery, University of Leipzig, An den Tierkliniken 21, 04103 Leipzig, Germany.
authors.forename: Walter
authors.identifier: 0000-0002-2601-9450
authors.initials: W
authors.lastname: Brehm
authors.affiliation: Translational Centre for Regenerative Medicine, University of Leipzig, Philipp-Rosenthal-Strasse 55, 04103 Leipzig, Germany; Department of Pathology and Laboratory Medicine, Tulane University, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Heller
authors.affiliation: Large Animal Clinic for Surgery, University of Leipzig, An den Tierkliniken 21, 04103 Leipzig, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Pfeiffer
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190 Vienna, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Kasper