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

Background. All human islets used in research and for the clinical hreatment of diabetes are subject to iseh damage during pancreias procurement. preservation, and islet isdaon. A major factor influencing islet function is exposure of pancreata to od ischernia during unavoidable windows of preservation by static cold storage (SCS). Improved preservation metbods may prevent this functonal detedoration. In the present study, we investigated whether pancreas preservation by gaseous oxygen perfusion (persufflation) better preserved islet furicon versus SCS. Methods. Human pancreata were preserved by SCS or by persuffiaflon in combinailon with SCS. Islets were subsequenly islated, and preparations in each group matched for SCS ortoti preservation time were conpared using dynamic glucose-stimulated insulin secretion as a measure of 3-cell function and RNA sequendng to elucidate transcritomic chang Results. Persufflated pancret had reduced SCS time, which resulted in islets with higher glucose-stimulated insulin secretion compared to Wets from SCS only pancreata. RNA sequencing of islets from persufflated pancreata idenfied reduced inammatory and greater metabolic gene expression, consistent with expectations of reducing cold ischernic exposure. Portions of these tianscipatonal responses were not assoiated with time spent in SCS and were attributable to pancreatic reoxygenatlen. Furthemore, persuffation extended the total preservation time by 50% without any detectable dectne in islet function or viability. ConcluSions. These data demonstrate that pancreas preservation by persufflation rather than SCS before Wet isdation reduces irilammatory responses and promotes metabolic pathways in human islets, which results in improved beta cel function.