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Inflammatory biomarkers in the blood and pancreatic tissue of organ donors that predict human islet isolation success and function.
Islets 2020; :1-11I

Abstract

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.

Authors+Show Affiliations

Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of the City of Hope, Duarte, CA, USA. Department of Hematopoietic Cell Transplantation and T Cell Therapy, City of Hope National Medical Center, Duarte, CA, USA.Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of the City of Hope, Duarte, CA, USA.Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of the City of Hope, Duarte, CA, USA.Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of the City of Hope, Duarte, CA, USA.Department of Surgery, Division of Transplantation, University of California Irvine Medical Center, Orange, CA, USA.Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of the City of Hope, Duarte, CA, USA.Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of the City of Hope, Duarte, CA, USA.Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of the City of Hope, Duarte, CA, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31935153

Citation

Oancea, Alina R., et al. "Inflammatory Biomarkers in the Blood and Pancreatic Tissue of Organ Donors That Predict Human Islet Isolation Success and Function." Islets, 2020, pp. 1-11.
Oancea AR, Omori K, Orr C, et al. Inflammatory biomarkers in the blood and pancreatic tissue of organ donors that predict human islet isolation success and function. Islets. 2020.
Oancea, A. R., Omori, K., Orr, C., Rawson, J., Dafoe, D. C., Al-Abdullah, I. H., ... Mullen, Y. (2020). Inflammatory biomarkers in the blood and pancreatic tissue of organ donors that predict human islet isolation success and function. Islets, pp. 1-11. doi:10.1080/19382014.2019.1696127.
Oancea AR, et al. Inflammatory Biomarkers in the Blood and Pancreatic Tissue of Organ Donors That Predict Human Islet Isolation Success and Function. Islets. 2020 Jan 14;1-11. PubMed PMID: 31935153.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inflammatory biomarkers in the blood and pancreatic tissue of organ donors that predict human islet isolation success and function. AU - Oancea,Alina R, AU - Omori,Keiko, AU - Orr,Chris, AU - Rawson,Jeffrey, AU - Dafoe,Donald C, AU - Al-Abdullah,Ismail H, AU - Kandeel,Fouad, AU - Mullen,Yoko, Y1 - 2020/01/14/ PY - 2020/1/15/entrez PY - 2020/1/15/pubmed PY - 2020/1/15/medline KW - Islet transplantation KW - donor factors KW - inflammatory biomarker KW - inflammatory cytokines SP - 1 EP - 11 JF - Islets JO - Islets N2 - 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. SN - 1938-2022 UR - https://www.unboundmedicine.com/medline/citation/31935153/Inflammatory_biomarkers_in_the_blood_and_pancreatic_tissue_of_organ_donors_that_predict_human_islet_isolation_success_and_function L2 - http://www.tandfonline.com/doi/full/10.1080/19382014.2019.1696127 DB - PRIME DP - Unbound Medicine ER -