Leiden University Medical Center
Good functionality but lower yield after islet isolation from donation after circulatory death Pancreata
Jason B Doppenberg1, Hein Putter2, Michiel F Nijhoff1, Marten A Engelse1, Eelco JP de Koning1,3.
1Internal Medicine, Leiden University Medical Center, Leiden, Netherlands; 2Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, Netherlands; 3Diabetes and Islet Neogenesis, Hubrecht Institute for Development Biology and Stem Cell Research, Utrecht, Netherlands
Donation after circulatory death (DCD) is increasingly performed due to a shortage of donation after brain death (DBD) organs. However, organ function may be reduced due to the warm ischemia time. We investigated the use of DCD pancreata for islet isolation and transplantation.
Islet isolation procedures from 192 DBD and 93 DCD donor pancreata between 2008-2014 were studied. Donor and procurement characteristics were compared between DBD and DCD groups and were corrected for mismatched covariates (UNIANOVA), such as age, gender, BMI, cold ischemia time, height, glucose, type of perfusate, hypotensive period, chronological quintile, and vasopressor usage. IEQ, purity, and volumes were quantified after every isolation, and repeated on consecutive medium changes. IEQs after isolation and medium changes were determined in a repeated measures model (Mixed Model). Dynamic glucose stimulated insulin secretion tests were performed on islets considered for clinical transplantation. Since 2011 DCD islets were used in human transplantation procedures in combination with DBD islets. Three months after transplantation mixed meal tests were performed.
DBD islet isolations had a larger final product volume (+26.8µL±4.38, p= 0.014), maximum purity (+5.00%±2.01, p=0.013) and IEQ/g (+73.72±8.25, p=0.003). Islet yield differed significantly after isolation (day 0) (437,603 IEQ for DBD islets and 343,418 for DCD islets). After medium changes IEQ was 378,470 (day 1) and 294,715 (day 3) for DBD islets and 291,279 (day 1) and 218,444 (day 3) for DCD islets (p=0.011 for DBD vs. DCD IEQs and p<0.001 for IEQ change per day). Importantly, the percentage decrease in IEQ from day 0 to 1 and day 0 to 3 did not differ between DBD and DCD groups (p=0.478, p=0.732). Warm Ischemia times particular to DCD procurement were analyzed in intervals, but were not found to relate to obtained IEQ. Insulin secretion was not different between DBD and DCD islets (peak stimulation index: 4.6±0.3, n=82 for DBD and 5.4±1.3, n=13 for DCD islets, p=NS; AUC 397.9 for DBD and 412.1 for DCD islets, p=NS). Transplantations using single DBD grafts, two DBD grafts simultaneously, or combined DBD and DCD grafts, showed no difference in AUC C-peptide/(IEQ/kg recipient) in mixed meal tests (p=0.077).
After correction of relevant variables there was an increased yield and purity of DBD islets. However, after subsequent culture the relative decrease in islet number was similar.
In conclusion, isolations from DCD pancreata generated a lower yield compared to DBD donor pancreata but resulted in similar functionality. DCD islets should be considered for use in transplantation.
15:30 - 17:00
|Pancreas & Islet Donors: Assessing Risk and Optimizing Outcomes||Good functionality but lower yield after islet isolation from donation after circulatory death Pancreata||Room 110|
15:30 - 17:00
|Islet Quality Assessment and Engraftment||Preliminary results of isolated islets after hypothermic machine perfusion of human donor pancreata||Plenary Room 1|