Panzer, J.K. ; Hiller, H.* ; Cohrs, C.M. ; Almaça, J.* ; Enos, S.J. ; Beery, M.* ; Cechin, S.* ; Drotar, D.M. ; Weitz, J.R.* ; Santini, J.* ; Huber, M.K.* ; Muhammad Fahd Qadir, M.* ; Pastori, R.L.* ; Domínguez-Bendala, J.* ; Phelps, E.A.* ; Atkinson, M.A.* ; Pugliese, A.* ; Caicedo, A.* ; Kusmartseva, I.* ; Speier, S.
Pancreas tissue slices from organ donors enable in situ analysis of type 1 diabetes pathogenesis.
JCI insight 5:134525 (2020)
In type 1 diabetes (T1D), autoimmune destruction of pancreatic beta cells leads to insulin deficiency and loss of glycemic control. However, knowledge about human pancreas pathophysiology in T1D remains incomplete. To address this limitation, we established a pancreas tissue slice platform of donor organs with and without diabetes, facilitating the first live cell studies of human pancreas in T1D pathogenesis to our knowledge. We show that pancreas tissue slices from organ donors allow thorough assessment of processes critical for disease development, including insulin secretion, beta cell physiology, endocrine cell morphology, and immune infiltration within the same donor organ. Using this approach, we compared detailed pathophysiological profiles for 4 pancreata from donors with T1D with 19 nondiabetic control donors. We demonstrate that cell loss, beta cell dysfunction, alterations of beta cell physiology, and islet infiltration contributed differently to individual cases of T1D, allowing insight into pathophysiology and heterogeneity of T1D pathogenesis. Thus, our study demonstrates that organ donor pancreas tissue slices represent a promising and potentially novel approach in the search for successful prevention and reversal strategies of T1D.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Autoimmune Diseases ; Autoimmunity ; Beta Cells ; Diabetes ; Endocrinology; Alpha-cell-function; Nod Mouse Model; Animal-models; Beta-cells; Islet; Onset; Morphology; Expression; Langerhans; Insulitis
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Language
english
Publication Year
2020
Prepublished in Year
HGF-reported in Year
2020
ISSN (print) / ISBN
2379-3708
e-ISSN
2379-3708
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Volume: 5,
Issue: 8,
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Article Number: 134525
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Clarivate
Publishing Place
Ann Arbor, Michigan
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Reviewing status
Peer reviewed
Institute(s)
Institute of Pancreatic Islet Research (IPI)
POF-Topic(s)
90000 - German Center for Diabetes Research
Research field(s)
Helmholtz Diabetes Center
PSP Element(s)
G-502600-005
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Copyright
Erfassungsdatum
2020-05-06