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

Amy C. Kelly, Kate E. Smith, William G. Purvis, Catherine G. Min, Craig S. Weber, Amanda M. Cooksey, Craig Hasilo, Steven Paraskevas, Thomas M. Suszynski, Bradley P. Weegman, Miranda J. Anderson, Leticia E. Camacho, Robert C. Harland, Thomas Loudovaris, Jana Jandova, DIana S. Molano, Nicholas D. Price, Ivan G. Georgiev, William E. Scott, Derek M.D. ManasJames A.M. Shaw, Doug O'Gorman, Tatsuya Kin, Fiona M. McCarthy, Gregory L. Szot, Andrew M. Posselt, Peter G. Stock, Theodore Karatzas, A. M.James Shapiro, Ronald M. Lynch, Sean W. Limesand, Klearchos K. Papas

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)160-167
Number of pages8
Issue number1
StatePublished - Jan 1 2019
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health grants NIH/SBIR 5R44DK070400-04 (K.K.P., Co-Principal Investigator with Dr. Linda Templeman, Giner Inc.) and R01DK084842 (S.W.L., Principal Investigator) and NIH/NIDDK DP3 grant 1DP3DK106933-01 (K.K.P., Principal Investigator).

Publisher Copyright:
© Wolters Kluwer Health, Inc. All rights reserved.


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