09/H0606/16

Oxfordshire REC C

University of Oxford

Oxford Tissue Bank for Studies of Metabolic Disease

Oxford Tissue Bank for Studies of Metabolic Disease

Professor Mark McCarthy
OCDEM,
Churchill Hospital,
Headington, Oxford. OX3 7LJ

01865 857 298

mark.mccarthy@drl.ox.ac.uk

In our current ongoing study involving 500 participants for which we had a favourable opinion from Oxfordshire Research Ethics Committee B and R&D approval until 2010 under the original ethics project 05/Q1605/148, we have, and will continue to collect, the following:-

SAMPLES:-

BODY SITES INVOLVED:-

From patients undergoing surgery at the Oxford Radcliffe Hospitals NHS Trust, who have consented, we are collecting biopsies of:-

- fat (subcutaneous, omental, mesenteric)
- skeletal muscle
- liver sections (but only where liver resection is already planned on clinical grounds)
- pancreas (but only where pancreatic resection is already planned on clinical grounds)
- blood samples for DNA extraction, serum and plasma for storage and assays of biochemical traits

Please note that all acquisition of biopsies and samples is designed to be consistent with the elective surgical procedure planned. There is no additional injury or risk of bleeding further to that of the planned operative procedure required to be carried out by the surgeons.

Please also note that for the liver tissue and the pancreatic tissue, these will only be acquired where the resection of these organs is planned as part of the elective surgical procedure.

FORMATS:-

For the past two years of the current research study we have been collecting these tissues in a variety of formats according to the research objectives:-

1) Tissues to be used for the generation of tissue micro-arrays are collected into formalin in theatre, histoprocessed down to paraffin embedded tissue donor blocks and stored in our research laboratory until required by our research partners. In this form, they can be safely stored for many years without degradation.

2) Tissues for storage in the Biobank are snap frozen into liquid nitrogen in theatre and stored in the liquid nitrogen store. In this form, they can be safely stored in perpetuity.

3) Optionally, tissues for other research purposes may be preserved in other media, according to the protocol.

4) Blood is collected in vacutainer tubes in theatre, processed and then the fractions are stored at minus 80 degrees in our research laboratory freezers.

ESTIMATED NUMBER OF SAMPLES TO BE STORED:-

Over the past two years from 100 research participants we have generated 400 paraffin embedded tissue donor blocks to support the generation of recipient donor blocks for the tissue micro-arrays.They comprise the following:-
- 106 donor blocks of abdominal subcutaneous fat (including 20 diabetic samples)
- 101 donor blocks of abdominal muscle (including 20 diabetic samples)
- 104 donor blocks of omental fat (including 20 diabetic samples)
- 55 donor blocks of mesenteric fat (including 10 diabetic samples)
- 21 donor blocks of liver tissue (including 2 diabetic samples)
- 13 donor blocks of pancreatic tissue (including 3 diabetic samples)

From these same 100 research participants, we have also collected and have stored 1,190 aliquots of tissue snap frozen and stored in our liquid nitrogen stores in OCDEM.These aliquots equate to:-

- 335 of subcutaneous fat (60 diabetic samples)
- 300 of abdominal muscle (50 diabetic samples)
- 310 of omental fat (55 diabetic samples)
- 163 of mesenteric fat (25 diabetic samples)
- 65 of liver tissue (7 diabetic samples)
- 17 of pancreatic (3 diabetic samples)
These have been widely used by our research partners.

We also have blood from these 100 research participants stored at minus 80 degrees in the freezers in our research laboratories in OCDEM in the following manner:

- 100 x 10ml. tube of whole blood (1 per research participant)
- 100 x buffy coat aliquots for DNA (1 per research participant)
- 300 x plasma aliquots (3 per research participant)
- 300 x serum aliquots (3 per research participant)


At a rough estimate, we would anticipate that annually we would collect tissues from 50 research participants. Therefore,we would estimate the acquisition of samples to be roughly half of those described above would be added to the collection at an annual rate.



DATA:-

Please refer to our answer to 10-1.

N/A

The McCarthy group, and the other members of international consortia with whom they collaborate, are interested in the identification and characterisation of the molecular basis of diabetes, obesity and related conditions. This work involves a range of complementary approaches including large scale gene analysis and the use of animal models. In addition, the group and its collaborators make use of human tissues for studies of mRNA and protein expression of genes and proteins relevant to their research objectives. This work involves both systematic quantitative research (e.g. on large numbers of adipose tissue samples collected by subcutaneous biopsy in standardised coditions) as well as semi quantitative studies of tissue expression in a wider range of tissues. The Tissue Bank, which is the subject of this approval, pertains only to the latter. As we have done in the past two years, we wish to use the Tissue Bank to generate tissue samples that can be used for semi quantitative studies of RNA and protein expression, through for example, real-time polymerase chain reaction (RT PCR) or immunochemical (tissue microarray) methods.

These studies are designed to establish whether RNAs or proteins of interest are expressed in tissues of relevance to Type 2 Diabetes and obesity, and to gain some initial understanding of possible relationships between expressed levels and disease status. Samples taken at surgery provide the only feasible means for such studies in man (especially for inaccessible tissues such as omental and mesenteric fat, liver and pancreatic tissue), and complement equivalent studies in tissues from suitable animal models. Naturally the particular circumstances of collection ( comorbidity, individual variation, medication, anaesthesia etc., introduce substantial variability between samples that precludes detailed statistical analysis (unless many thousands of samples were collected). Nevertheless, we have direct experience of the value of semiquantitative analyses based on existing samples collected over the past two years which support our assertion that the Tissue Bank is of scientific value.

PUBLICITY:-

Our research tissue biobank is designed exclusively for the use of our departmental researchers and their collaborators. We have no intention to advertise wider usage as this is a finite resource and these existing arrangements ensure full use.

SENSITIVE NATURE OF USE OF TISSUES:-

All data are anonymised before analysis. All uses are as specified in the consent.

APPLICATION FOR ACCESS TO SAMPLES:-

All applications to access to tissues are through the custodian of the collection, Professor Mark McCarthy. Access is restricted to collaborators within established consortia.

POLICIES FOR FINANCIAL DEALINGS RELATED TO SUPPLY OF SAMPLES AND DATA:-

No financial transactions are envisaged.

POLICIES FOR ACCOUNTABILITY TO DONORS:-

All samples and data are anonymized before use.

Please refer to our answer to Question 11.

Favourable Opinion