Does islet size really influence graft function following clinical islet transplantation?

Background It has been proposed that islet transplants comprised primarily of small rather than large islets may provide better graft function, due to their lower susceptibility to hypoxic damage. Our aim was to determine whether islet size correlated with in vivo graft function in islet transplant recipients with C peptide negative type 1 diabetes when islets have undergone pretransplant islet culture. Methods Human pancreatic islets were isolated, cultured for 24hours and infused by standardised protocols. 90 min-stimulated C-peptide concentrations were determined during a standard meal tolerance test 3 months posttransplant. The islet isolation index (IEq/islet number) was determined immediately after isolation and again before transplantation (after tissue culture). This was correlated with patient insulin requirement or stimulated C-peptide. Results Changes in insulin requirement did not significantly correlate with islet isolation index. Stimulated C-peptide correlated weakly with IEq at isolation (p=0.40) and significantly with IEq at transplantation (p=0.018). Stimulated C-peptide correlated with islet number at isolation (p=0.013) and more strongly with the islet number at transplantation (p=0.001). In contrast, the correlation of stimulated C-peptide and islet isolation index was weaker (p=0.018) and this was poorer at transplantation (p=0.034). Using linear regression, the strongest association with graft function was islet number (r=0.722, p=0.001). Islet size was not related to graft function after adjusting for islet volume or number. Conclusion These data show no clear correlation between islet isolation index and graft function; both small and large islets are suitable for transplantation provided the islets have survived a short culture period postisolation. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Corresponding author: SJ Hughes; stephen.hughes@nds.ox.ac.uk (44 (0)1865 857507). Islet Lab, Nuffield Department of Surgical Sciences, OCDEM Building, Churchill Hospital, Headington Oxford OX3 7LE The authors declare no conflict of interest. Stephen J Hughes participated in research design, data analysis and manuscript preparation Paul A Bateman participated in data analysis and manuscript preparation Sarah E Cross participated in manuscript preparation Daniel Brandhorst participated in manuscript preparation Heide Brandhorst participated in manuscript preparation Ioannis Spiliotis participated in data analysis and manuscript preparation Chitra Ballav participated in manuscript preparation Miranda Rosenthal participated in manuscript preparation Martin K Rutter participated in data analysis and manuscript preparation James Shaw participated in manuscript preparation Stephen Gough participated in manuscript preparation Paul RV Johnson participated in research design and manuscript preparation Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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