09/H0606/11

Oxfordshire REC C

Nuffield Department of Orthopaedics, Rheumatology & Muskuloskeletal Sciences, University of Oxford

Oxford Musculoskeletal Tissue Bank (OMB)

Oxford Musculoskeletal Tissue Bank - A resource for research into the pathobiology of bone, joint and soft tissue diseases

Nigel Arden
Professor in Rheumatic Diseases
Director of Musculoskeletal Epidemiology and Biobank: University of Oxford and Southampton
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences
Botnar Research Centre
Old Road
OXFORD OX3 7LD

01865 227357

nigel.arden@ndorms.ox.ac.uk

Samples of neoplastic and non-neoplastic disorders of bone, joint and soft tissues comprise the main specimens held in the bio bank. All samples are either surplus to diagnostic requirements or would otherwise be discarded at the time of surgery. Samples of blood, urine and tissue fluids (e.g. synovial fluid) are also collected and stored. Most stored samples will be snap frozen and stored in -80 degrees freezer units or in liquid nitrogen vessels. Some samples will be fixed in 10% formalin. Some of the formalin fixed samples may be subsequently processed and embedded in wax blocks.Some samples are processed for immediate cell or tissue culture and are either used directly in experiments or expanded in culture and cryogenically stored for later re-culture. All of these samples can be kept indefinately if storage protocols are adhered to and optimal storage conditions maintained.

All data storage will be stored on a dedicated inventory database. Data will be obtained from the patient's medical record but will be made anonymous by the database manager. The data will include gender, date of birth, details of operation and diagnosis. In addition, we collect an outstanding amount of phenotypic data.

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The Oxford Musculoskeletal BioBank is a resource aimed at research groups that are studying neoplastic and non-neoplastic disorders of bone joint and soft tissue. Primarily, this resource is aimed at research groups working within the Botnar Research Centre and the Nuffield Orthopaedic Centre. In addition, we would like to promote this resource nationally to external collaborators and research groups from external institutions.

In order to study these disease processes, human tissue is required, and through close collaboration with the Nuffield Orthopaedic Centre, we propose to collect samples from operations performed there. Most orthopaedic research units share a similar symbiotic relationship with their local hospital.

All samples obtained are tissues that are either normally disposed of at the time of surgery: cartilage, bone, synovium, synovial fluid, bone marrow, and tendon; or are surplus to diagnostic requirements: tumour samples, normal tissue samples. In both cases the patients care remains the same and their diagnosis is in no way compromised.

In addition to samples obtained during a surgical procedures we would also like to routinely collect samples of blood and urine which will enable the BioBank to supplement the data held for each donor.

In summary, the OMB is an NRES approved research tissue bank which holds its own HTA licence for the storage of human tissue for the purpose research. We were inspected in September 2010 and received very positive and encouraging feedback. We have facilities to collect, process and store human blood, urine and intra operative or diagnostic "waste" tissue, i.e. tissue that would ordinarily be disposed of. In addition, we collect an outstanding amount of phenotypic data. Our goal is to recruit all patients that attend the NOC for medical and surgical care.

Only appropriately consented patients will be entered into the BioBank.

We operate a controlled access policy and any applications for access to material are scrutinised and reviewed by the OMB access committee to ensure end use falls within the scope of our own ethical boundaries.
All research groups that wish to use the BioBank must apply through the OMB Access Committee. Only projects that are covered by the scope of this application will be authorised. In addition to obtaining approval from the Access Committee, if a research group wishes to start their own sub-collection or enter an existing collection under the cover of the Oxford Musculoskeletal BioBank, the researcher must provide evidence that they comply to the BioBank's policies on storage, health & safety, disposal, security, quality management, access, training and consent. Evidence can be in the form of Standard Operating Procedures. These policies have been put in place to ensure HTA compliance.

Tissue and data will only be released to external research groups if they hold appropriate ethics committee approval and all transfers will be made with a Material Transfer Agreement in place.

The BioBank intends to support the following research interests:
1.Investigating the causes of disease, damage and degeneration in musculoskeletal cells and tissues

2.Examining the unique effects of the bone marrow microenvironment on bone-seeking cancers and primary musculoskeletal tumours

3.Developing assays to determine the in vivo role of growth factors, hypoxia, angiogenesis, matrix attachment and cytokine response signalling pathways in disease and repair of musculoskeletal tissues and in relevant tumours

4.Establishing novel culture methodologies for generating distinct musculoskeletal cell types from sources including blood and tissue.

5.Examining the relationship between assay findings and response to therapy and pathological variables in musculoskeletal tissues and primary tumours.

6.Establishing methods to discriminate structure-function relationships based on mechanical testing and biochemical composition of tissues

7.Developing and validating 3-dimensional models of tissue explanted intact or reconstructed on grafts and implants for initial use in establishing necessary assays for studying 3D, mechanically loaded musculoskeletal cells and later to mechanically and biochemically characterise these prior to clinical trial.

8.Developing and validating models to predict responses to novel adjuvant treatments and agents, whether these directly target musculoskeletal tissues or cause damaging side-effects in the skeleton.

9.Searching for evidence of age and disease-relevant epigenetic modifications in musculoskeletal tissue and investigating the mechanisms.

10.Analysing tissue for disease-causing somatic mutations that are tissue-specific or chimeric and not expressed in blood.

11.Developing non-invasive measuring tools to assess mechanical properties and early damage or repair markers to more appropriately target preventative strategies and to rapidly assess response to novel treatments and side-effects on musculoskeletal tissues.

12.Pharmacodynamic and pharmacokinetic monitoring of drugs or therapeutic agents eg. monoclonal antibodies, in early phase trials

13.Providing the mechanistic information to apply in Phase III trials of new agents, to select the right patients for therapy and so improve outcomes and cost effectiveness.

14.Continue to build on our long-term relationships with industry to investigate novel agents in early phase trials
15. To study the natural history of treated and untreated musculoskeletal conditions and develop assessment tools to predict outcome based on clinical data, biomarkers and imaging markers
16. To develop new diagnostic tools using bio-specimens.

Favourable Opinion

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