RESUMEN
Multipotent mesenchymal stem cells (MSCs) have enormous potential in tissue engineering and regenerative medicine. However, until now, their development for clinical use has been severely limited as they are a mixed population of cells with varying capacities for lineage differentiation and tissue formation. Here, we identify receptor tyrosine kinase-like orphan receptor 2 (ROR2) as a cell surface marker expressed by those MSCs with an enhanced capacity for cartilage formation. We generated clonal human MSC populations with varying capacities for chondrogenesis. ROR2 was identified through screening for upregulated genes in the most chondrogenic clones. When isolated from uncloned populations, ROR2+ve MSCs were significantly more chondrogenic than either ROR2-ve or unfractionated MSCs. In a sheep cartilage-repair model, they produced significantly more defect filling with no loss of cartilage quality compared with controls. ROR2+ve MSCs/perivascular cells were present in developing human cartilage, adult bone marrow, and adipose tissue. Their frequency in bone marrow was significantly lower in patients with osteoarthritis (OA) than in controls. However, after isolation of these cells and their initial expansion in vitro, there was greater ROR2 expression in the population derived from OA patients compared with controls. Furthermore, osteoarthritis-derived MSCs were better able to form cartilage than MSCs from control patients in a tissue engineering assay. We conclude that MSCs expressing high levels of ROR2 provide a defined population capable of predictably enhanced cartilage production. Stem Cells 2017;35:2280-2291.
Asunto(s)
Condrogénesis/genética , Células Madre Mesenquimatosas/metabolismo , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/genética , Proteína Wnt-5a/genética , Animales , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Humanos , Receptores Huérfanos Similares al Receptor Tirosina Quinasa/metabolismo , Ovinos , Ingeniería de Tejidos , Proteína Wnt-5a/metabolismoRESUMEN
An ovine total hip arthroplasty model was developed to evaluate metal ion release, wear, the biological response and adverse tissue reaction to metal-on-metal (MoM) bearing materials. The performance of an advanced superlattice ceramic coating (SLC) was evaluated as a bearing surface and experimental groups divided into; (1) MoM articulating surfaces coated with a SLC coating (SLC-MoM), (2) uncoated MoM surfaces (MoM), and (3) metal on polyethylene (MoP) surfaces. Implants remained in vivo for 13 months and blood chromium (Cr) and cobalt (Co) metal ion levels were measured pre and postoperatively. Synovial tissue was graded using an ALVAL scoring system. When compared with the MoM group, sheep with SLC-MoM implants showed significantly lower levels of chromium and cobalt metal ions within blood over the 13-month period. Evidence of gray tissue staining was observed in the synovium of implants in the MOM group. A significantly lower ALVAL score was measured in the SLC-MoM group (3.88) when compared with MoM components (6.67) (p = 0.010). ALVAL results showed no significant difference when SLC-MOM components were compared to MoP (5.25). This model was able to distinguish wear and the effect of released debris between different bearing combinations and demonstrated the effect of a SLC coating when applied onto the bearing surface. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1760-1771, 2019.