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

Autor: Dyson NJ; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Kattner N; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Honkanen-Scott M; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Hunter B; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., Doyle JA; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom., White K; Electron Microscopy Research Services, Newcastle University, Newcastle upon Tyne, United Kingdom., Davey TS; Electron Microscopy Research Services, Newcastle University, Newcastle upon Tyne, United Kingdom., Ploeg RJ; Nuffield Department of Surgical Science, John Radcliffe Hospital, Oxford, United Kingdom., Bury YA; Department of Cellular Pathology, Royal Victoria Infirmary, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Tiniakos DG; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.; Department of Pathology, Aretaieion Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Shaw JAM; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.; Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom., Scott WE 3rd; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Jazyk: angličtina
Zdroj: Transplantation direct [Transplant Direct] 2021 Dec 16; Vol. 8 (1), pp. e1271. Date of Electronic Publication: 2021 Dec 16 (Print Publication: 2022).
DOI: 10.1097/TXD.0000000000001271
Abstrakt: 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 islet isolation with utility for unbiased evaluation of acute stress in organ transplantation research.
(Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)
Databáze: MEDLINE
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