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Open Access Beneficial Effects of Ischemic Preconditioning on Pancreas Cold Preservation

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Ischemic preconditioning (IPC) confers tissue resistance to subsequent ischemia in several organs. The protective effects are obtained by applying short periods of warm ischemia followed by reperfusion prior to extended ischemic insults to the organs. In the present study, we evaluated whether IPC can reduce pancreatic tissue injury following cold ischemic preservation. Rat pancreata were exposed to IPC (10 min of warm ischemia followed by 10 min of reperfusion) prior to ∼18 h of cold preservation before assessment of organ injury or islet isolation. Pancreas IPC improved islet yields (964 ± 336 vs. 711 ± 204 IEQ/pancreas; p = 0.004) and lowered islet loss after culture (33 ± 10% vs. 51 ± 14%; p = 0.0005). Islet potency in vivo was well preserved with diabetes reversal and improved glucose clearance. Pancreas IPC reduced levels of NADPH-dependent oxidase, a source of reactive oxygen species, in pancreas homogenates versus controls (78.4 ± 45.9 vs. 216.2 ± 53.8 RLU/μg; p = 0.002). Microarray genomic analysis of pancreata revealed upregulation of 81 genes and downregulation of 454 genes (greater than twofold change) when comparing IPC-treated glands to controls, respectively, and showing a decrease in markers of apoptosis and oxidative stress. Collectively, our study demonstrates beneficial effects of IPC of the pancreas prior to cold organ preservation and provides evidence of the key role of IPC-mediated modulation of oxidative stress pathways. The use of IPC of the pancreas may contribute to increasing the quality of donor pancreas for transplantation and to improving organ utilization.

Keywords: Cold ischemia; Cold preservation; Ischemic preconditioning; Islets of Langerhans; Microarrays; NADPH oxidase; NADPH-dependent superoxide (NOX); Oxidative stress; Pancreas; Rat; Transcriptome

Document Type: Research Article


Affiliations: Diabetes Research Institute, University of Miami, Miami, FL, USA

Publication date: July 1, 2012

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.

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