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

用于研究 SARS-CoV-2/COVID-19 病理生理学和糖尿病的内分泌体外模型

• 批准号: 458701159
• 负责人: Professor Dr. Alexander Kleger
• 金额: --
• 依托单位: Institut für Molekulare Virologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2021
• 资助国家: 德国
• 起止时间: 2020-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/458701159?language=en
• 关键词: Endocrine; vitro; models; study; pathophysiology

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.

已知严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）主要感染呼吸道，但也会对肾脏、心脏、大脑和胃肠道器官造成直接伤害。此外，SARS-CoV-2似乎直接损害胰岛素代谢感染，而2019冠状病毒病（COVID-19）本身的病程受到糖尿病的影响。到目前为止，尚不清楚SARS-CoV-2是否选择性地靶向和感染β细胞并影响其功能，如果是，则以何种方式影响。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表明，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，这种不适合移植的胰岛的可用性有限，价格昂贵，制备质量和纯度往往较低。此外，供体的多样性和有限的材料需要多种胰岛制备才能产生可靠的结果。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，以了解COVID-19患者糖尿病的发病机制。