Pancreas / islet

In this project, the pancreas may be perfused with ABO group-matched blood on an ex vivo normothermic perfusion rig to study pancreas and duodenum physiology, as well as ischaemia reperfusion injury and therapeutic approaches for its amelioration.

Histopathological examination and analysis of the pancreas will be used to determine suitability of the pancreas for transplantation as well as pathogenesis of diabetes.

Biopsies from the pancreas will also be used for the development of stem cell-based therapies for the treatment of diabetes, such as pancreatic organoids.

Single cell genomic analysis of the pancreas will be used to gain insights into the embryological development of the pancreas and the mutation burden in the normal organ which may predispose to development of cancers.

• Full Title: A study of the pancreas function, physiology, pathology and therapeutics
• Start Date: 1st October 2012
• Sponsor Organisation: University of Cambridge
• ODT Study Number: 3

Insulin-producing and other cells will be separated and purified from donated pancreases. The specific objectives are:

• to maintain islet viability and function in vitro and in vivo following pancreas retrieval; isolation at a geographically distant site and return to retrieval centre for transplantation
• to optimise islet viability and function by establishment in culture prior to transplantation
• to increase functional β-cell mass for transplantation by growth factor and culture condition manipulation to prevent apoptosis; enhance β-cell function; and induce proliferation
• to reduce β-cell immunogenicity to limit the need for immunosuppression after transplantation
• to develop standard operating procedures for safe clinical transplantation of islets
  
  

• Full Title: Process development for islet isolation targeted at enhancing islet yield and viability
• Start Date: 20th September 2005
• Sponsor Organisation: Newcastle University
• ODT Study Number: 20
• Specialist Nurse Team facilitating study-specific consent: Northern (and Yorkshire, when cross-covering)

This study can receive pancreases that have been removed for transplantation and then deemed unsuitable. These pancreases are offered to studies such as this one through the National Allocation Scheme.

This study can also receive pancreases from organ donors where their pancreases have been deemed untransplantable before removal (e.g. they are diabetic), and their family have given consent.

Removal of the pancreas specifically for this research study can only occur in selected local hospitals:

• Freeman Hospital, Newcastle
• Royal Victoria Infirmary, Newcastle
• James Cook University Hospital, Middlesbrough
• Friarage Hospital, Northallerton
• Sunderland Royal Hospital, Sunderland
• Darlington Memorial Hospital, Darlington
• University of North Durham Hospital, Durham

This study seeks to optimise islet transplantation by developing ways to support long-term graft survival.

• Full Title: A pre-clinical study of human islet function to improve long-term graft survival 
• Start Date: 1st July 2013
• Sponsor Organisation: Worcestershire Acute Hospitals NHS Trust
• ODT Study Number: 34

The group have established a method that enables the preparation of de-cellularised tissues and organs form the digestive tract, which can be used as a scaffold to repopulate with cultured human gastrointestinal cells of both cell line and primary origin.

The 3D human disease platform will allows the team to investigate the underlying pathophysiology of digestive tract diseases.

• Full Title: Organ Regeneration and Disease Modelling using a 3D biological scaffold
• Start Date: 3rd March 2014
• Sponsor Organisation: University College London
• ODT Study Number: 50

This study is investigating the use of automated technologies to increase islet transplantability, and investigating other modifications to existing protocols to increase islet yield.

• Full Title: Use of deceased donor pancreata to optimise and improve the clinical islet isolation process in a research environment 
• Start Date: 3rd June 2019
• Sponsor Organisation: Scottish National Blood Transfusion Service (SNBTS)
• ODT Study Number: 85

Diabetes affects 3.3 million UK patients costing £8.7 billion per year.

Type 1 Diabetes is caused by loss of insulin production by the islets of Langerhans found in the pancreas.

Treatment involves regular injections of insulin or in selected cases by replacement of the islets by transplanting new islets. Islet replacement has been hampered by the inefficiency of islet transplantation and rejection of the islets once transplanted.

Currently islets are collected from the pancreas of dead donors, processed in the laboratory and then transplanted into the patient by injecting them into the portal venous blood system of the liver.

On contact with blood 25-80% of the islets are destroyed by an inflammatory reaction. The surviving islets have to establish a new blood supply in the hostile environment of the liver whilst under attack from the patient’s immune system.

Despite taking immune suppressant medication, the patient’s immune system recognises these cells originating from someone else as foreign and tries to eliminate them. This immune attack further diminishes the number of islets that survive transplantation. The patient’s protective mechanisms are so good and the ability of the islets to colonise so poor, that islets from two to four pancreases may be needed in order to obtain sufficient successful islet colonies to produce enough insulin in the patient.

This project aims to establish if elimination of the initial inflammatory and immune response will enhance islet colonization.

Elimination of the inflammatory and immune response will be achieved by introducing islets into autogenous tissue in a laboratory.

The immune response won’t happen as the islets will be in their own body’s tissue and the inflammatory response won’t happen as the tissue is perfused by blood solution free of inflammation.

In this friendly environment, we hope to show that most of the islets will engraft and colonise.

• Full Title: Development of an ex-vivo endocrine pancreas for the investigation and treatment of diabetes
• Start Date: 3rd July 2019
• Sponsor Organisation: University of Oxford
• ODT Study Number: 82

New technology means that it is becoming easier and easier to identify the genes that cause certain diseases.

Unfortunately, identifying a gene doesn't explain how it causes the disease. This requires a lot of laboratory work using cell and animal models.

However, animal models only tell us how things work in the animals that we use, and to see if a finding is true in humans, it is important to look in human tissue.

• Full Title: Identification of genes involved in renal, electrolyre and urinary tract disorders
• Start Date:1st April 2014
• Sponsor Organisation: University College London
• ODT Study Number: 40