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Pancreatic ischaemia associated with deceased organ donation negatively impacts whole\u2010organ and isolated\u2010islet transplantation outcomes. <jats:italic>Post\u2010mortem<\/jats:italic> changes have also hampered accurate interpretation of <jats:italic>ante\u2010mortem<\/jats:italic> pancreatic pathology. A rigorous histological scoring system accurately quantifying ischaemia is required to experimentally evaluate innovations in organ preservation and to increase rigour in clinical\/research evaluation of underlying pancreatic pathology. We developed and validated an unbiased electron microscopy (EM) score of acute pancreatic exocrine cellular stress in deceased organ donor cohorts (development [<jats:italic>n<\/jats:italic> =\u200928] and validation [<jats:italic>n<\/jats:italic> =\u200916]). Standardised assessment led to clearly described numerical scores (0\u20133) for nuclear, mitochondrial and endoplasmic reticulum (ER) morphology and intracellular vacuolisation; with a maximum (worst) aggregate total score of 12. In the Validation cohort, a trend towards higher scores was observed for tail versus head regions (nucleus score following donation after brainstem death [DBD]: head 0.67\u2009\u00b1\u20090.19; tail 0.86\u2009\u00b1\u20090.11; <jats:italic>p<\/jats:italic> =\u20090.027) and donation after circulatory death (DCD) versus DBD (mitochondrial score: DCD (head\u2009+\u2009tail) 2.59\u2009\u00b1\u20090.16; DBD (head\u2009+\u2009tail) 2.38\u2009\u00b1\u20090.21; <jats:italic>p<\/jats:italic> =\u20090.004). Significant mitochondrial changes were seen ubiquitously even with short cold ischaemia, whereas nuclear and vacuolisation changes remained mild even after prolonged ischaemia. ER score correlated with cold ischaemia time (CIT) following DBD (pancreatic tail region: <jats:italic>r<\/jats:italic> =\u20090.796; <jats:italic>p<\/jats:italic> =\u20090.018). No relationships between CIT and EM scores were observed following DCD. In conclusion, we have developed and validated a novel EM score providing standardised quantitative assessment of subcellular ultrastructural morphology in pancreatic acinar cells. This provides a robust novel tool for gold standard measurement of acute cellular stress in studies evaluating surrogate measures of peri\u2010transplant ischaemia, organ preservation technologies and in samples obtained for detailed pathological examination of underlying pancreatic pathology.<\/jats:p>","DOI":"10.1002\/cjp2.185","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T02:06:52Z","timestamp":1606097212000},"page":"173-187","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Development and validation of a quantitative electron microscopy score to assess acute cellular stress in the human exocrine pancreas"],"prefix":"10.1002","volume":"7","author":[{"given":"Nicole","family":"Kattner","sequence":"first","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Dyson","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Bury","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University  Newcastle upon Tyne UK"},{"name":"Department of Cellular Pathology, Royal Victoria Infirmary Newcastle upon Tyne Hospitals NHS Foundation Trust  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Tiniakos","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University  Newcastle upon Tyne UK"},{"name":"Department of Pathology, Aretaieion Hospital, Medical School National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"White","sequence":"additional","affiliation":[{"name":"Electron Microscopy Research Services Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"Davey","sequence":"additional","affiliation":[{"name":"Electron Microscopy Research Services Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Eliasson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Malm\u00f6, Islet Cell Exocytosis, Lund University Diabetes Centre Lund University  Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Tindale","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology, Royal Victoria Infirmary Newcastle upon Tyne Hospitals NHS Foundation Trust  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart E","family":"Wagner","sequence":"additional","affiliation":[{"name":"Histopathology Department Royal Hallamshire Hospital  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minna","family":"Honkanen\u2010Scott","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Doyle","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rutger J","family":"Ploeg","sequence":"additional","affiliation":[{"name":"Nuffield Department of Surgical Science University of Oxford, BRC Oxford and NHS Blood and Transplant  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James AM","family":"Shaw","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University  Newcastle upon Tyne UK"},{"name":"Institute of Transplantation, Freeman Hospital Newcastle upon Tyne Hospitals NHS Foundation Trust  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"William E","family":"Scott","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0963689718785629"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-1345(00)02479-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2007.01799.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2012.04075.x"},{"key":"e_1_2_8_6_1","unstructured":"NHSBT. 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