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Inflammatory biomarkers in the blood and pancreatic tissue of organ donors that predict human islet isolation success and function.
Islets ( IF 1.9 ) Pub Date : 2020-01-14 , DOI: 10.1080/19382014.2019.1696127
Alina R Oancea 1, 2 , Keiko Omori 1 , Chris Orr 1 , Jeffrey Rawson 1 , Donald C Dafoe 3 , Ismail H Al-Abdullah 1 , Fouad Kandeel 1 , Yoko Mullen 1
Affiliation  

The pancreas of brain-dead donors is the primary source of islets for transplantation. However, brain death mediates systemic inflammation, which may affect the quantity and quality of isolated islets. Our aim was to identify inflammatory biomarkers in donor blood and/or pancreatic tissue capable of predicting islet isolation success. Blood samples were collected from 21 pancreas donors and 14 healthy volunteers. Pancreatic tissue samples were also collected from the corresponding donor during organ procurement. Six serum cytokines were measured by a fluorescent bead-based immunoassay, and the expression of fifteen inflammatory target genes was quantified by quantitative reverse transcription polymerase chain reaction (RT-qPCR). There was no correlation between serum inflammatory cytokines and mRNA expression of the corresponding genes in peripheral blood mononuclear cells (PBMCs) or pancreatic tissue. The IL6 expression in pancreatic tissue correlated negatively with post-isolation islet yield. Islets isolated from donors highly expressing IFNG in PBMCs and MAC1 in pancreatic tissue functioned poorly in vivo when transplanted in diabetic NODscid mice. Furthermore, the increased MAC1 in pancreatic tissue was positively correlated with donor hospitalization time. Brain death duration positively correlated with higher expression of IL1B in PBMCs and TNF in both PBMCs and pancreatic tissue but failed to show a significant correlation with islet yield and in vivo function. The study indicates that the increased inflammatory genes in donor pancreatic tissues may be considered as biomarkers associated with poor islet isolation outcome.

中文翻译:

器官供体血液和胰腺组织中的炎性生物标志物可预测人胰岛分离的成功和功能。

脑死亡供者的胰腺是胰岛移植的主要来源。但是,脑死亡会介导全身性炎症,这可能会影响孤立的胰岛的数量和质量。我们的目的是在供体血液和/或胰腺组织中鉴定能够预测胰岛分离成功的炎症生物标志物。从21位胰腺供体和14位健康志愿者那里采集了血液样本。在器官采购期间还从相应的供体中收集了胰腺组织样品。通过基于荧光珠的免疫测定法测量了六种血清细胞因子,并通过定量逆转录聚合酶链反应(RT-qPCR)定量了十五种炎症靶基因的表达。外周血单个核细胞(PBMC)或胰腺组织中血清炎症细胞因子与相应基因的mRNA表达之间没有相关性。胰腺组织中IL6的表达与分离后胰岛的产量负相关。从供体中分离出的胰岛当移植到糖尿病NODscid小鼠体内时,其胰岛组织中PBMC和MAC1中高表达IFNG的体内功能较差。此外,胰腺组织中MAC1的增加与供体住院时间呈正相关。脑死亡持续时间与PBMC和胰腺组织中PBMC和TNF中IL1B的高表达呈正相关,但未显示与胰岛产量和体内功能显着相关。
更新日期:2020-01-14
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