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

Lookup NU author(s): Dr Bill ScottORCiD, Professor Derek Manas, Professor James Shaw

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Abstract

BACKGROUND: All 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. METHODS: Human 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. RESULTS: Persufflated 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. CONCLUSIONS: These 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.

Publication metadata

Author(s): Kelly AC, Smith KE, Purvis WG, Min CG, Weber CS, Cooksey AM, Hasilo C, Paraskevas S, Suszynski TM, Weegman BP, Anderson MJ, Camacho LE, Harland RC, Loudovaris T, Jandova J, Molano DS, Price ND, Georgiev IG, Scott WE, Manas DMD, Shaw JAM, O'Gorman D, Kin T, McCarthy FM, Szot GL, Posselt AM, Stock PG, Karatzas T, Shapiro AMJ, Lynch RM, Limesand SW, Papas KK

Publication type: Article

Publication status: Published

Journal: Transplantation

Year: 2019

Volume: 103

Issue: 1

Pages: 160-167

Online publication date: 01/01/2019

Acceptance date: 08/08/2018

ISSN (print): 0041-1337

ISSN (electronic): 1534-6080

Publisher: Lippincott Williams & Wilkins, Ltd.

URL: https://doi.org/10.1097/TP.0000000000002400

DOI: 10.1097/TP.0000000000002400

PubMed id: 30095738

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