Oxygen Perfusion (Persufflation) of Human Pancreata Enhances Insulin Secretion and Attenuates Islet Proinflammatory Signaling

• Published in: Transplantation Vol. 103; no. 1; pp. 160 - 167
• Main Authors: Kelly, Amy C, Smith, Kate E, Purvis, William G, Min, Catherine G, Weber, Craig S, Cooksey, Amanda M, Hasilo, Craig, Paraskevas, Steven, Suszynski, Thomas M, Weegman, Bradley P, Anderson, Miranda J, Camacho, Leticia E, Harland, Robert C, Loudovaris, Thomas, Jandova, Jana, Molano, Diana S, Price, Nicholas D, Georgiev, Ivan G, Scott, William E, Manas, Derek M.D, Shaw, James A.M, OʼGorman, Doug, Kin, Tatsuya, McCarthy, Fiona M, Szot, Gregory L, Posselt, Andrew M, Stock, Peter G, Karatzas, Theodore, Shapiro, A.M James, Lynch, Ronald M, Limesand, Sean W, Papas, Klearchos K
• Format: Journal Article
• Language: English
• Published: United States Copyright Wolters Kluwer Health, Inc. All rights reserved 01-01-2019
• Subjects: Adolescent; Adult; Cell Survival - drug effects; Cold Temperature; Energy Metabolism - drug effects; Female; Gene Expression Regulation - drug effects; Humans; Inflammation Mediators - metabolism; Insulin - metabolism; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Male; Middle Aged; Organ Preservation - adverse effects; Organ Preservation - methods; Oxygen - pharmacology; Perfusion - methods; Secretory Pathway - drug effects; Signal Transduction - drug effects; Time Factors; Tissue and Organ Harvesting; Young Adult
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/TP.0000000000002400

BACKGROUNDAll human islets used in research and for the clinical treatment of diabetes are subject to ischemic damage during pancreas procurement, preservation, and islet isolation. A major factor influencing islet function is exposure of pancreata to cold ischemia during unavoidable windows of preservation by static cold storage (SCS). Improved preservation methods may prevent this functional deterioration. In the present study, we investigated whether pancreas preservation by gaseous oxygen perfusion (persufflation) better preserved islet function versus SCS.
METHODSHuman pancreata were preserved by SCS or by persufflation in combination with SCS. Islets were subsequently isolated, and preparations in each group matched for SCS or total preservation time were compared using dynamic glucose-stimulated insulin secretion as a measure of β-cell function and RNA sequencing to elucidate transcriptomic changes.
RESULTSPersufflated pancreata had reduced SCS time, which resulted in islets with higher glucose-stimulated insulin secretion compared to islets from SCS only pancreata. RNA sequencing of islets from persufflated pancreata identified reduced inflammatory and greater metabolic gene expression, consistent with expectations of reducing cold ischemic exposure. Portions of these transcriptional responses were not associated with time spent in SCS and were attributable to pancreatic reoxygenation. Furthermore, persufflation extended the total preservation time by 50% without any detectable decline in islet function or viability.
CONCLUSIONSThese data demonstrate that pancreas preservation by persufflation rather than SCS before islet isolation reduces inflammatory responses and promotes metabolic pathways in human islets, which results in improved β cell function.