title: Human chondroprogenitors in alginate-collagen hybrid scaffolds produce stable cartilage in vivo.
abstract: The goal of this study was to evaluate human epiphyseal chondroprogenitor cells (ECPs) as a potential new cell source for cartilage regeneration. ECPs were compared to human bone marrow stromal cells (MSCs) and human adult articular chondrocytes (ACs) for their chondrogenic potential and phenotypic stability in vitro and in vivo. The cells were seeded in Optimaix-3D scaffolds at 5 × 104cells/mm3and gene expression, matrix production and mechanical properties were analysed up to 6 weeks. In vitro, ECPs synthesized consistently high collagen 2 and low collagen 10. AC-seeded constructs exhibited high donor variability in GAG/DNA values as well as in collagen 2 staining, but showed low collagen 10 production. MSCs, on the other hand, expressed high levels of collagen 2 but also of collagens 1 and 10, and were therefore not considered further. In vivo, there was considerable loss of matrix proteins in ECPs compared to in vitro cultured samples. To overcome this, a second implantation study investigated the effect of mixing cells with alginate prior to seeding in the scaffold. ECPs in alginate maintained their cartilage matrix and resisted mineralization and vessel infiltration better 6 weeks after subcutaneous implantation, whereas ACs lost their chondrogenic matrix completely. This study shows the great potential of ECPs as an off-the-shelf, highly chondrogenic cell type that produces stable cartilage in vivo. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Cartilage Engineering and Regeneration, Institute for Biomechanics, Swiss Federal Institute of Technology Zürich (ETH Zürich), Zürich, Switzerland.|Cellular and Molecular Bioengineering Research Laboratory, Department of Chemical and Petroleum Engineering, University of Calgary, Canada.
authors.forename: Deborah
authors.initials: D
authors.lastname: Studer
authors.affiliation: Cartilage Engineering and Regeneration, Institute for Biomechanics, Swiss Federal Institute of Technology Zürich (ETH Zürich), Zürich, Switzerland.
authors.forename: Emma
authors.initials: E
authors.lastname: Cavalli
authors.affiliation: Cartilage Engineering and Regeneration, Institute for Biomechanics, Swiss Federal Institute of Technology Zürich (ETH Zürich), Zürich, Switzerland.
authors.forename: Florian A
authors.initials: FA
authors.lastname: Formica
authors.affiliation: Institute for Biomechanics and ETH Phenomics Centre (EPIC), ETH Zürich, Switzerland.
authors.forename: Gisela Anne
authors.initials: GA
authors.lastname: Kuhn
authors.affiliation: Schulthess Klinik, Zürich, Switzerland.
authors.forename: Gian
authors.initials: G
authors.lastname: Salzmann
authors.affiliation: Department of Biomedicine, University Hospital Basel, Switzerland.
authors.forename: Marcus
authors.initials: M
authors.lastname: Mumme
authors.affiliation: Sport Clinic Zürich Hirslanden, Zürich, Switzerland.
authors.forename: Matthias R
authors.initials: MR
authors.lastname: Steinwachs
authors.affiliation: Department of Musculoskeletal Medicine, Regenerative Therapy Unit, University Hospital of Lausanne (CHUV), Epalinges, Switzerland.
authors.forename: Lee Ann
authors.initials: LA
authors.lastname: Laurent-Applegate
authors.affiliation: Laboratory for Biointerfaces, Empa, Swiss Federal Laboratories for Materials Testing and Research, St.Gallen, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Maniura-Weber
authors.affiliation: Cartilage Engineering and Regeneration, Institute for Biomechanics, Swiss Federal Institute of Technology Zürich (ETH Zürich), Zürich, Switzerland.
authors.forename: Marcy
authors.initials: M
authors.lastname: Zenobi-Wong
mesh_terms: D000328:Adult; D000464:Alginates / Q000737:chemistry / Q000494:pharmacology; D002356:Cartilage / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D003094:Collagen / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry / Q000494:pharmacology; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020723:Glucuronic Acid; D003094:Collagen
keywords: allogeneic; cartilage regeneration; chondrocytes; chondroprogenitors; collagen scaffold; mesenchymal stromal cells