title: Validation of Islet Transport From a Geographically Distant Isolation Center Enabling Equitable Access and National Health Service Funding of a Clinical Islet Transplant Program for England.
abstract: Islet transplantation has become established as a successful treatment for type 1 diabetes complicated by recurrent severe hypoglycemia. In the UK access has been limited to a few centrally located units. Our goal was to validate a quality-assured system for safe/effective transport of human islets in the UK and to successfully undertake the first transplants with transported islets. Pancreases were retrieved from deceased donors in the north of England and transported to King's College London using two-layer method (TLM) or University of Wisconsin solution alone. Islets were isolated and transported back to Newcastle in standard blood transfusion or gas-permeable bags with detailed evaluation pre- and posttransport. In the preclinical phase, islets were isolated from 10 pancreases with mean yield of 258,000 islet equivalents. No significant differences were seen between TLM and University of Wisconsin solution organ preservation. A significant loss of integrity was demonstrated in islets shipped in gas-permeable bags, whereas sterility, number, purity, and viability were maintained in blood transfusion bags. Maintenance of secretory granules and glucose-stimulated insulin secretion was confirmed following transport. A Standard Operating Procedure enabling final pretransplant quality control from a simple side-arm sample was validated. Moreover, levels of insulin and cytokines in transport medium were low, enabling transplant without centrifugation/resuspension at the recipient site. Six clinical transplants of transported islets were undertaken in five recipients with 100% primary graft function and resolution of severe hypoglycemia. Safe and clinically effective islet transport has been established facilitating sustainable NHS funding of a clinical islet transplant program for the UK.
authors.affiliation: Institute of Cellular Medicine, Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Ali
authors.initials: A
authors.lastname: Aldibbiat
authors.affiliation: † Division of Diabetes and Nutritional Sciences, King's College London , London , UK.
authors.forename: Guo Cai
authors.initials: GC
authors.lastname: Huang
authors.affiliation: † Division of Diabetes and Nutritional Sciences, King's College London , London , UK.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Institute of Cellular Medicine, Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Graham N
authors.initials: GN
authors.lastname: Holliman
authors.affiliation: Institute of Cellular Medicine, Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Linda
authors.initials: L
authors.lastname: Ferguson
authors.affiliation: ‡ Nuffield Department of Surgical Sciences, University of Oxford , Oxford , UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Hughes
authors.affiliation: § Department of Haematology, Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Ken
authors.initials: K
authors.lastname: Brigham
authors.affiliation: ¶ Institute of Transplantation, Freeman Hospital , Newcastle upon Tyne , UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Wardle
authors.affiliation: ¶ Institute of Transplantation, Freeman Hospital , Newcastle upon Tyne , UK.
authors.forename: Rob
authors.initials: R
authors.lastname: Williams
authors.affiliation: § Department of Haematology, Newcastle University , Newcastle upon Tyne , UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Dickinson
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK; ¶Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Steven A
authors.initials: SA
authors.lastname: White
authors.affiliation: ‡ Nuffield Department of Surgical Sciences, University of Oxford , Oxford , UK.
authors.forename: Paul R V
authors.initials: PR
authors.lastname: Johnson
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK; ¶Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Manas
authors.affiliation: † Division of Diabetes and Nutritional Sciences, King's College London , London , UK.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Amiel
authors.affiliation: Institute of Cellular Medicine, Newcastle University , Newcastle upon Tyne , UK.
authors.forename: James A M
authors.initials: JA
authors.lastname: Shaw
keywords: Glucose-stimulated insulin secretion; Islet isolation; Islet transplant; Islet transport; Type 1 diabetes