title: Engineered Microtissues Formed by Schiff Base Crosslinking Restore the Chondrogenic Potential of Aged Mesenchymal Stem Cells.
abstract: A universal method for reproducibly directing stem cell differentiation remains a major challenge for clinical applications involving cell-based therapies. The standard approach for chondrogenic induction by micromass pellet culture is highly susceptible to interdonor variability. A novel method for the fabrication of condensation-like engineered microtissues (EMTs) that utilizes hydrophilic polysaccharides to induce cell aggregation is reported here. Chondrogenesis of mesenchymal stem cells (MSCs) in EMTs is significantly enhanced compared to micromass pellets made by centrifugation measured by type II collagen gene expression, dimethylmethylene blue assay, and histology. MSCs from aged donors that fail to differentiate in pellet culture are successfully induced to synthesize cartilage-specific matrix in EMTs under identical media conditions. Furthermore, the EMT polysaccharides support the loading and release of the chondroinduction factor transforming growth factor β3 (TGF-β3). TGF-β-loaded EMTs (EMT(+TGF) ) facilitate cartilaginous tissue formation during culture in media not supplemented with the growth factor. The clinical potential of this approach is demonstrated in an explant defect model where EMT(+TGF) from aged MSCs synthesize de novo tissue containing sulfated glycosaminoglycans and type II collagen in situ.
authors: Cartilage Engineering + Regeneration Laboratory, ETH Zürich, Otto-Stern-Weg 7, 8093, Zürich, Switzerland.
authors: Christopher
authors: C
authors: Millan
authors: Cartilage Engineering + Regeneration Laboratory, ETH Zürich, Otto-Stern-Weg 7, 8093, Zürich, Switzerland.
authors: Emma
authors: E
authors: Cavalli
authors: Biomedical Materials Group, Martin Luther University Halle-Wittenberg, Heinrich-Damerow-Strasse 4, 06120, Halle (Saale), Germany.
authors: Thomas
authors: T
authors: Groth
authors: Laboratory for Biointerfaces, Empa, Swiss Federal Laboratories for Materials Science and Technology, Lerchenfeldstrasse 5, 9014, St. Gallen, Switzerland.
authors: Katharina
authors: K
authors: Maniura-Weber
authors: Cartilage Engineering + Regeneration Laboratory, ETH Zürich, Otto-Stern-Weg 7, 8093, Zürich, Switzerland.
authors: Marcy
authors: M
authors: Zenobi-Wong
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D002356:Cartilage / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D002454:Cell Differentiation; D002478:Cells, Cultured; D020219:Chondrogenesis; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D012545:Schiff Bases; D023822:Tissue Engineering
chemical_list: D012545:Schiff Bases
keywords: Schiff base; aging; chondrogenesis; mesenchymal stem cells; microtissues