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2017 - IPITA

Clinical Islet Allo-transplantation 1

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

Presenter: Steve, Hughes, Oxford, United Kingdom
Authors: Stephen Hughes, Paul Bateman, Sarah Cross, Daniel Brandhorst, Heide Brandhorst, Miranda Rosenthal, Martin Rutter, James Shaw, Stephen Gough, Paul Johnson

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

S. Hughes1, P. Bateman1, S. Cross1, D. Brandhorst1, H. Brandhorst1, M. Rosenthal2, M. Rutter3, J. Shaw4, S. Gough5, P. Johnson1.

1Nuffield Department of Surgical Sciences, Oxford University, Oxford, UK, ; 2UCL Institute of Immunity and Transplantation, University College London, London, UK, ; 3Endocrinology and Diabetes Research Group, Manchester University, Manchester, UK, ; 4Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK, ; 5Radcliffe Department of Medicine, Oxford University, Oxford, UK,

Aims of Study: Previous studies have postulated that islet transplants comprised of small rather than large diameter islets may provide better graft function, due to their lower susceptibility to hypoxic damage. However, such studies used islets transplanted immediately after isolation which may have influenced the results. Our aim was to determine whether islet size correlated with in vivo measurements of islet graft function following a single islet tranplant in recipients with C-peptide negative type 1 diabetes in which islets had undergone a period of pre-tranplant culture.
Methods: With appropriate consent and ethical approval, human pancreases were retrieved, islets isolated and cultured for 24 hours and then prepared for infusion according to standardised protocols. Recipients were transplanted following percutaneous catheterisation of the portal vein, under standard immuno- suppression protocols with insulin requirements monitored as part of routine clinical care. In a sub-group of recipients 90 min-stimulated C-peptide concentrations were determined during a standard meal tolerance test 3 months post-transplant (n=19). The islet isolation index (number of islet equivalents-IEq/islet number) was determined as a measure of average islet size immediately after isolation and following 24 hours in culture at transplantation and correlated with the stimulated C-peptide level. Data was expressed as mean ± SD and analysed statistically by Pearson’s correlation and linear regression.
Results: In islet grafts, the mean±SD number of IEq after isolation and at transplantation were 454,800±190,900 and 408,600±126,700 respectively whereas the islet number at isolation and at transplantation was 232,320±114,060 and 197,300±91,200 respectively. Purity ranged from 50-90% and was viability ≥ 75% in all cases. The mean 3-month post-transplant stimulated C-peptide concentration was 624±524 pmol/L. Stimulated C-peptide showed no significant correlation with IEq/kg body weight at isolation (r= 0.057, p=0.411) although this became significant at transplantation (r= 0.494, p=0.018). The strongest correlation with stimulated C-peptide was with islet number at isolation (r=0.525, p=0.013) which became even stronger at transplantation (r=0.722, p=0.001) In contrast, the correlation of the islet isolation index with stimulated C-peptide (pmol/L/IEQ/kg body weight) was weaker and was poorer at transplantation (r= -0.439, p=0.034) than at isolation (r= -0.495, p=0.018). Regression analysis was performed to investigate the independent relationships of size and number on stimulated C-peptide. This showed:

Effect   on Stimulated C-peptide

P   value





Islet number/ kg



IEQ/kg + Islet number/kg



IEQ/ Islet number



Conclusion: These data show there is no strong correlation between islet isolation index and islet graft function, meaning that both small and large islets are equally suitable for transplantation provided they have survived a short culture period post- isolation.

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