Endocrine in vitro models to study pathophysiology and diabetes in SARS-CoV-2/COVID-19

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)已知主要感染呼吸道，但也会对肾脏、心脏、脑和胃肠道器官造成直接损害。此外，SARS-CoV-2似乎直接损害胰岛素代谢感染，而冠状病毒病程2019年(新冠肺炎)本身受到糖尿病的影响。到目前为止，还不清楚SARS-CoV-2是否选择性地瞄准和感染β细胞，并影响它们的功能，如果是的话，以何种方式。此外，不同器官对SARS-CoV-2感染的细胞反应机制可能不同。我们实验室的初步数据显示，缺乏足够移植质量的朗格汉斯人胰岛可以有效地感染SARS-CoV-2。然而，这种无移植能力的胰岛可获得性有限，价格非常昂贵，而且制备质量和纯度往往较低。此外，捐赠者的多样性和受限制的材料需要多次胰岛准备才能产生强劲的结果。因此，本项目的总体目标是利用干细胞来源的胰腺内分泌细胞作为模型系统，研究SARS-CoV-2的感染和复制情况，以了解新冠肺炎患者糖尿病的发病机制。

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is known to infect mostly the respiratory tract but also causes direct injury in kidneys, heart, brain, and gastrointestinal organs. Furthermore, SARS-CoV-2 appears to directly compromise the insulin metabolism infection while the course of coronavirus disease 2019 (COVID-19) itself is impacted by diabetes mellitus. So far, it is unclear whether SARS-CoV-2 selectively targets and infects beta-cells and affects their function and if so, in which way. Moreover, cellular response mechanisms towards SARS-CoV-2 infection might differ across various organs. Preliminary data from our labs show that human islets of Langerhans lacking sufficient quality for transplantation can be productively infected with SARS-CoV-2. However, such transplantation-incompetent islets have limited availability, are very expensive and often render with low preparation quality and purity. Moreover, donor diversity and restricted material requires multiple islet preparations to generate robust results. Therefore, the overall aim of this project is to employ stem cell-derived pancreatic endocrine cells as model system to investigate SARS-CoV-2 infection and replication in order to understand the diabetes pathogenesis in COVID-19 patients.