Inflammatory biomarkers in the blood and pancreatic tissue of organ donors that predict human islet isolation success and function.
Inflammatory biomarkers in the blood and pancreatic tissue of organ donors that predict human islet isolation success and function.
复制标题
器官捐献者血液和胰腺组织中的炎症生物标志物，可预测人类胰岛分离的成功和功能。
DOI：
10.1080/19382014.2019.1696127
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发表时间：
2020
期刊：
影响因子：
2.2
通讯作者：
Mullen,Yoko
中科院分区：
文献类型：
--
作者：
Oancea,AlinaR;Omori,Keiko;Orr,Chris;Rawson,Jeffrey;Dafoe,DonaldC;Al-Abdullah,IsmailH;Kandeel,Fouad;Mullen,Yoko
脑死亡供体的胰腺是移植胰岛的主要来源。然而，脑死亡介导全身炎症，这可能会影响分离的胰岛的数量和质量。我们的目的是鉴定供体血液和/或胰腺组织中能够预测胰岛分离成功的炎症生物标志物。从21名胰腺供体和14名健康志愿者收集血液样品。在器官获取过程中，还从相应供体采集胰腺组织样本。通过基于荧光珠的免疫测定法测量6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15种炎症靶基因的表达。外周血单个核细胞（PBMCs）和胰腺组织中相应基因的mRNA表达与血清炎症细胞因子之间无相关性。胰腺组织中IL 6的表达与分离后胰岛产量呈负相关。从PBMC中高表达IFNG和胰腺组织中高表达MAC 1的供体分离的胰岛移植到糖尿病NODscid小鼠体内时功能不佳。胰腺组织中MAC 1的升高与供体住院时间呈正相关。脑死亡时间与PBMC中IL 1和TNF的高表达呈正相关，但与胰岛产量和体内功能无显著相关性。本研究表明，供者胰腺组织中炎性基因的增加可能被认为是与胰岛分离效果差相关的生物标志物。
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. TheIL6expression in pancreatic tissue correlated negatively with post-isolation islet yield. Islets isolated from donors highly expressingIFNGin PBMCs andMAC1in pancreatic tissue functioned poorlyin vivowhen transplanted in diabetic NODscidmice. Furthermore, the increasedMAC1in pancreatic tissue was positively correlated with donor hospitalization time. Brain death duration positively correlated with higher expression ofIL1Bin PBMCs andTNFin both PBMCs and pancreatic tissue but failed to show a significant correlation with islet yield andin vivofunction. The study indicates that the increased inflammatory genes in donor pancreatic tissues may be considered as biomarkers associated with poor islet isolation outcome.