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

Lookup NU author(s): Professor James Shaw



This is the authors' accepted manuscript of an article that has been published in its final definitive form by Lippincott Williams & Wilkins, 2018.

For re-use rights please refer to the publisher's terms and conditions.


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 pre-transplant 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 post-transplant. 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 post-isolation.

Publication metadata

Author(s): Hughes SJ, Bateman PA, Cross SE, Brandhorst D, Brandhorst H, Spiliotis I, Ballav C, Rosenthal M, Rutter MK, Shaw J, Gough S, Johnson PRV

Publication type: Article

Publication status: Published

Journal: Transplantation

Year: 2018

Volume: 102

Issue: 11

Pages: 1857-1863

Print publication date: 01/11/2018

Online publication date: 30/07/2018

Acceptance date: 07/06/2018

Date deposited: 24/07/2018

ISSN (print): 0041-1337

ISSN (electronic): 1534-6080

Publisher: Lippincott Williams & Wilkins


DOI: 10.1097/TP.0000000000002392


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Funder referenceFunder name
BDA 06/0003362
EU Horizon 20/20 grant