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J Tissue Eng Regen Med. 2017 Nov;11(11):3014-3026. doi: 10.1002/term.2203. Epub 2016 Jul 4.

Human chondroprogenitors in alginate-collagen hybrid scaffolds produce stable cartilage in vivo.

Author information

1
Cartilage Engineering and Regeneration, Institute for Biomechanics, Swiss Federal Institute of Technology Zürich (ETH Zürich), Zürich, Switzerland.
2
Cellular and Molecular Bioengineering Research Laboratory, Department of Chemical and Petroleum Engineering, University of Calgary, Canada.
3
Institute for Biomechanics and ETH Phenomics Centre (EPIC), ETH Zürich, Switzerland.
4
Schulthess Klinik, Zürich, Switzerland.
5
Department of Biomedicine, University Hospital Basel, Switzerland.
6
Sport Clinic Zürich Hirslanden, Zürich, Switzerland.
7
Department of Musculoskeletal Medicine, Regenerative Therapy Unit, University Hospital of Lausanne (CHUV), Epalinges, Switzerland.
8
Laboratory for Biointerfaces, Empa, Swiss Federal Laboratories for Materials Testing and Research, St.Gallen, Switzerland.

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 × 104 cells/mm3 and 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.

KEYWORDS:

allogeneic; cartilage regeneration; chondrocytes; chondroprogenitors; collagen scaffold; mesenchymal stromal cells

PMID:
27373220
DOI:
10.1002/term.2203
[Indexed for MEDLINE]

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