THE REGULATION OF NEUTROPHIL EXTRACELLULAR TRAPS (NETS) BY ADENOSINE IN MYOCARDIAL ISCHEMIA-REPERFUSION

腺苷在心肌缺血再灌注中对中性粒细胞胞外陷阱（NETS）的调节

• 批准号: 10275147
• 负责人: Rebecca Diane Levit
• 金额: $ 7.83万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-23 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10275147
• 关键词: Adenosine; Adenosine Diphosphate; Adenosine Monophosphate; Allogenic; Anti-Inflammatory Agents; Autologous; Bone Marrow; Cells; Clinical Trials; Data; Disease; Evaluation; Human; Inflammation; Inflammatory; Lead; Membrane Proteins; Mesenchymal Stem Cells; Metabolism; Myocardial Ischemia; Play; Production; Proteins; Purines; Regulation; Reperfusion Therapy; Research; Role; Sex Differences; Therapeutic; Work; biological sex; clinical application; cytokine; extracellular; immunoregulation; in vivo; insight; lens; mesenchymal stromal cell; neutrophil; purine metabolism; sex; stem cell therapy

PROJECT SUMMARY The objective of the proposed research supplement is to understand how donor biologic sex impacts the level and functionality of surface protein, CD73, on human mesenchymal stem cells (hMSCs). This protein is essential in the metabolism of adenosine diphosphate (ADP) to anti-inflammatory adenosine (ADO). Some mechanisms underlying the immunomodulatory capabilities have been well described such as cytokine production, but others such as purine metabolism are understudied. We aim to understand the difference in purine metabolism by CD73 through the lens of donor sex in order to assess efficacy of hMSCs to mitigate an inflammatory state. hMSCs are able to mitigate inflammation in many disease states but have shown variability between donors in clinical trials. Our study will investigate how donor sex plays a role in CD73 expression, CD73 activity level, and cytokine production, another mechanism of hMSC action in vivo. Together these data will provide critical insight into sex- dependent differences in hMSC immunomodulation. This work is of importance because it will impact clinical application of hMSCs by (1) evaluation of cells for specific therapeutic applications, (2) selection of allogenic donors for broad application, (3) selecting candidates that would benefit from autologous hMSC therapeutics.

项目摘要 拟议的研究补充的目的是了解供体的生物性别如何影响水平 以及表面蛋白CD 73在人间充质干细胞（hMSC）上的功能。这种蛋白质是必需的 在腺苷二磷酸（ADP）代谢为抗炎腺苷（ADO）中。一些机制 已经很好地描述了潜在的免疫调节能力，例如细胞因子的产生，但其他 如嘌呤代谢研究不足。我们的目的是通过CD 73来了解嘌呤代谢的差异， 通过供体性别的透镜，以评估hMSC减轻炎症状态的功效。hMSCs 能够减轻许多疾病状态下的炎症，但在临床试验中显示出供体之间的差异性。 审判我们的研究将探讨供体性别如何在CD 73表达、CD 73活性水平和细胞因子中发挥作用。 生产，hMSC在体内作用的另一种机制。这些数据将为性行为提供重要的见解- hMSC免疫调节的依赖性差异。这项工作很重要，因为它将影响临床 通过（1）评估细胞的特异性治疗应用，（2）选择同种异体细胞， 供者广泛应用，（3）选择将受益于自体hMSC治疗的候选者。