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

项目总结 拟议的研究补充的目的是了解捐赠者的生物性别如何影响水平。 以及人骨髓间充质干细胞(HMSCs)表面蛋白CD73的功能。这种蛋白质是必不可少的。 在二磷酸腺苷(ADP)代谢为抗炎腺苷(ADO)的过程中。一些机制 潜在的免疫调节能力已经被很好地描述，如细胞因子的产生，但其他 例如嘌呤代谢的研究还不够深入。我们的目的是了解CD73在嘌呤代谢中的差异 通过供者性别的镜头，以评估hMSCs缓解炎症状态的效果。骨髓间充质干细胞 能够减轻许多疾病状态下的炎症，但在临床上表现出供者之间的差异 审判。我们的研究将调查供者性别对CD73表达、CD73活性水平和细胞因子的影响 产生，hMSC体内作用的另一种机制。综合起来，这些数据将提供对性的关键洞察-- HMSC免疫调节的依存性差异。这项工作很重要，因为它将影响临床 人骨髓间充质干细胞的应用：(1)评价特定治疗用途的细胞；(2)选择同种异体 广泛应用的供者；(3)选择将从自体hMSC疗法中受益的候选者。

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.