Pancreas tissue slices from organ donors enable in situ analysis of type 1 diabetes pathogenesis
Pancreas tissue slices from organ donors enable in situ analysis of type 1 diabetes pathogenesis
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DOI：
10.1172/jci.insight.134525
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发表时间：
2020-04-23
期刊：
影响因子：
8
通讯作者：
Speier, Stephan
中科院分区：
文献类型：
--
作者：
Panzer, Julia K.;Hiller, Helmut;Speier, Stephan
在 1 型糖尿病 (T1D) 中，胰腺 β 细胞的自身免疫性破坏导致胰岛素缺乏和血糖控制丧失。然而，关于 T1D 人类胰腺病理生理学的知识仍然不完整。为了解决这一限制，我们建立了患有和不患有糖尿病的供体器官的胰腺组织切片平台，据我们所知，促进了人类胰腺在 T1D 发病机制中的首次活细胞研究。我们表明，来自器官捐献者的胰腺组织切片可以对疾病发展的关键过程进行全面评估，包括胰岛素分泌、β细胞生理学、内分泌细胞形态和同一供体器官内的免疫浸润。使用这种方法，我们比较了 4 例 T1D 捐献者与 19 名非糖尿病对照捐献者的胰腺的详细病理生理学特征。我们证明，细胞丢失、β 细胞功能障碍、β 细胞生理学改变和胰岛浸润对 T1D 个体病例的影响不同，从而有助于深入了解 T1D 发病机制的病理生理学和异质性。因此，我们的研究表明，器官捐献者胰腺组织切片代表了寻找成功预防和逆转 T1D 策略的一种有前途且可能新颖的方法。
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.