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Lookup NU author(s): Nicola DysonORCiD, Dr Nicole Kattner, Minna Honkanen-Scott, Bethany Hunter, Jennifer Doyle, Dr Kathryn White, Tracey DaveyORCiD, Dr Yvonne BuryORCiD, Dr Dina Tiniakos, Professor James Shaw, Dr Bill ScottORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Background: Pancreas and islet transplantation outcomes are negatively impacted by injury to the endocrine cells from acute stress during donor death, organ procurement, processing, and transplant procedures. Here, we report a novel electron microscopy scoring system, the Newcastle Pancreas Endocrine Stress Score (NPESS). Methods: NPESS was adapted and expanded from our previously validated method for scoring pancreatic exocrine acinar cells, yielding a 4-point scale (0-3) classifying ultrastructural pathology in endocrine cell nuclei, mitochondria, endoplasmic reticulum, cytoplasmic vacuolization, and secretory granule depletion, with a maximum additive score of 15. We applied NPESS in a cohort of deceased organ donors after brainstem (DBD) and circulatory (DCD) death with a wide range of cold ischemic times (3.6-35.9 h) including 3 donors with type 1 and 3 with type 2 diabetes to assess islets in situ (n = 30) in addition to pancreata (n = 3) pre- and postislet isolation. Results: In DBD pancreata, NPESS correlated with cold ischemic time (head: r = 0.55; P = 0.02) and mirrored exocrine score (r = 0.48; P = 0.01). When stratified by endocrine phenotype, cells with granules of heterogeneous morphology had higher scores than α, β, and δ cells (P < 0.0001). Cells of mixed endocrine-exocrine morphology were observed in association with increased NPESS (P = 0.02). Islet isolation was associated with improved NPESS (in situ: 8.39 ± 0.77 [Mean ± SD]; postisolation: 5.44 ± 0.31; P = 0.04). Conclusions: NPESS provides a robust method for semiquantitative scoring of subcellular ultrastructural changes in human pancreatic endocrine cells in situ and following isle
Author(s): Dyson NJ, Kattner N, Honkanen-Scott M, Hunter B, Doyle JA, White K, Davey TS, Ploeg RJ, Bury YA, Tiniakos DG, Shaw JAM, Scott WE
Publication type: Article
Publication status: Published
Journal: Transplantation Direct
Year: 2022
Volume: 8
Issue: 1
Online publication date: 16/01/2022
Acceptance date: 05/12/2021
Date deposited: 26/01/2022
ISSN (electronic): 2373-8731
Publisher: Lippincott Williams & Wilkins
URL: https://doi.org/10.1097/TXD.0000000000001271
DOI: 10.1097/TXD.0000000000001271
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