P1 Large scale three-dimensional cartilage tissue engineering using adult bone marrow stem cells from OA patients

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Controlled expansion and differentiation of mesenchymal stem cells in a microcarrier based stirred bioreactor

Controlled expansion and differentiation of mesenchymal stem cells in a microcarrier based stirred bioreactor

The Wnt5a Receptor, Receptor Tyrosine Kinase-Like Orphan Receptor 2, Is a Predictive Cell Surface Marker of Human Mesenchymal Stem Cells with an Enhanced Capacity for Chondrogenic Differentiation

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 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 un-cloned 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 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 osteoarthritis 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. This article is protected by copyright. All rights reserved

Tissue Engineering of Fibrocartilaginous Tissues: The Intervertebral Disc and the Meniscus

The intervertebral disc in the spine and the meniscus in the knee are two fibrocartilaginous tissues which commonly are injured or become degenerate, causing significant clinical problems. The principals of tissue engineering, which are applicable elsewhere in the body, hold true for the disc and meniscus. Whilst there are some similarities with articular cartilage in terms of the molecules present, these fibrocartilages have their own peculiarities, some of which can be quite challenging. Following a description of the structure and anatomy of the disc and meniscus and the current clinical treatments, the different strategies for biological repair are described focusing particularly on cell therapy. The types of cells and scaffolds being investigated and how these can be modified are discussed

Cell-based Approaches to Joint Surface Repair : A Research Perspective

The authors are grateful for support to their research from Arthritis Research UK (grants 19271, 19429, 19667, 20050). None of the authors received any funding related to the writing of this manuscript, and the funding bodies did not play any role in the writing of the manuscript or decision to submit the manuscript for publication.Peer reviewedPublisher PD

The influence of HLA genotype on the development of metal hypersensitivity following joint replacement

\ua9 2022, The Author(s). Background: Over five million joint replacements are performed across the world each year. Cobalt chrome (CoCr) components are used in most of these procedures. Some patients develop delayed-type hypersensitivity (DTH) responses to CoCr implants, resulting in tissue damage and revision surgery. DTH is unpredictable and genetic links have yet to be definitively established. Methods: At a single site, we carried out an initial investigation to identify HLA alleles associated with development of DTH following metal-on-metal hip arthroplasty. We then recruited patients from other centres to train and validate an algorithm incorporating patient age, gender, HLA genotype, and blood metal concentrations to predict the development of DTH. Accuracy of the modelling was assessed using performance metrics including time-dependent receiver operator curves. Results: Using next-generation sequencing, here we determine the HLA genotypes of 606 patients. 176 of these patients had experienced failure of their prostheses; the remaining 430 remain asymptomatic at a mean follow up of twelve years. We demonstrate that the development of DTH is associated with patient age, gender, the magnitude of metal exposure, and the presence of certain HLA class II alleles. We show that the predictive algorithm developed from this investigation performs to an accuracy suitable for clinical use, with weighted mean survival probability errors of 1.8% and 3.1% for pre-operative and post-operative models respectively. Conclusions: The development of DTH following joint replacement appears to be determined by the interaction between implant wear and a patient’s genotype. The algorithm described in this paper may improve implant selection and help direct patient surveillance following surgery. Further consideration should be given towards understanding patient-specific responses to different biomaterials

The influence of HLA genotype on the development of metal hypersensitivity following joint replacement

We thank Innovate UK Edge for providing funding to allow this research to be carried out.Background  Over five million joint replacements are performed across the world each year. Cobalt chrome (CoCr) components are used in most of these procedures. Some patients develop delayed type hypersensitivity (DTH) responses to CoCr implants, resulting in tissue damage and revision surgery. DTH is unpredictable and genetic links have yet to be definitively established. Methods At a single site, we carried out an initial investigation to identify HLA alleles associated with development of DTH following metal-on-metal hip arthroplasty. We then recruited patients from other centres to train and validate an algorithm incorporating patient age, gender, HLA genotype44 and blood metal concentrations to predict the development of DTH. Accuracy of the modelling was assessed using performance metrics including time dependent receiver operator curves. Results Using next generation sequencing, here we determine the HLA genotypes of 606 patients. 176 of these patients had experienced failure of their prostheses; the remaining 430 remain asymptomatic at a mean follow up of twelve years. We demonstrate that the development of DTH is associated with patient age, gender, the magnitude of metal exposure and the presence of certain HLA class II alleles. We show that the predictive algorithm developed from this investigation performs to an accuracy suitable for clinical use, with weighted mean survival probability errors of 1.8% and 3.1%53 for pre-operative and post-operative models respectively. Conclusions The development of DTH following joint replacement appears to be determined by the interaction between implant wear and a patient’s genotype. The algorithm described in this paper may improve implant selection and help direct patient surveillance following surgery. Further consideration should be given towards understanding patient specific responses to different biomaterials.Publisher PDFPeer reviewe