STRO-4 immunoreactive progenitor cells from human bone marrow and articular cartilage – Isolation, characterisation and application in cartilage tissue engineering

Abstract

STRO-4+ chondrocytes significantly increased with articular cartilage degeneration (p=0.01) and clusters of cells in very degenerate articular cartilage were STRO-4 and STRO-1 immunoreactive and co-expressed the cell proliferation marker Ki-67. A small proportion (1.24% ± 0.39) of STRO-4+ HACs, isolated using fluorescence activated cell sorting, were able to demonstrate clonal expansion ability. The STRO-4+ single-cell derived clonal cell populations expressed the putative stem/progenitor cell markers STRO-1, CD105 and CD166, demonstrated tri-lineage differentiation ability and exhibited superior in vitro chondrogenic ability compared to donor-matched unselected HACs. Using an ex vivo organotypic co-culture assembly, 3D hyaline-like cartilage constructs generated by STRO-4+ single cell-derived clonal cell populations were able to repair a partial thickness articular cartilage defect with full integration of the neocartilaginous repair tissue with the native articular cartilage. Furthermore, the STRO-4+ single cell-derived clonal cell populations demonstrated robust ectopic bone formation in a subcutaneous murine model.
This is the first study to demonstrate that the STRO-4 antibody is able to identify a novel population of cartilage-derived progenitor cells with adult stem cell-like characteristics that exhibit superior in vitro chondrogenesis compared to donor-matched unselected HACs, robust repair of partial thickness articular cartilage defects and ectopic in vivo osteogenesis. This work proposes a tissue-based strategy for the repair of articular cartilage defects, which is a step-change transition from the current cell-based repair strategies, by demonstrating that cartilage constructs of human articular cartilage-derived STRO-4+ adult stem cell-like progenitor cells have the potential for the surgical repair of chondral and osteochondral defects; and paves the way for comprehensive in vivo studies in a suitable animal model in the future.

More information

Identifiers

ORCID for Howard Clementi Tribe: orcid.org/0000-0003-2011-4147

ORCID for Rahul Tare: orcid.org/0000-0001-8274-8837

ORCID for Richard Oreffo: orcid.org/0000-0001-5995-6726

Catalogue record

Export record