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Development and Application of a Semi quantitative Scoring Method for Ultrastructural Assessment of Acute Stress in Pancreatic Islets

Lookup NU author(s): Nicola Dyson, 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

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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


Publication metadata

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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Funding

Funder referenceFunder name
BB/R013942/1Biotechnology and Biological Sciences Research Council (BBSRC)
EP/M017559/1
IS-BTU-0214-10027
MR/R014132/1Medical Research Council (MRC)

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