Basaal II - P45 - Preliminary results of isolated islets after hypothermic machine per­fu­sion of human donor pancreata

M. Leemkuil, J.B. Doppenberg, R.J. Ploeg, C. Krikke, E.J.P de Koning, M.A. Engelse, H.G.D. Leuvenink

Chair(s): prof. dr. Carla C. Baan, Erasmus MC Rotterdam

Thursday 10 march 2016

12:30 - 13:00h at Foyer

Categories: Postersessie

Parallel session: Postersessies XI - Opgesplitst in 3 tijdblokken en 3 categoriëen (klinisch, basaal, donatie)

Background:
Islet transplantation is an effective treatment option for patients with type I diabetes mellitus. Due to the persistent shortage of good quality donor organs, pancreata from marginal donors are more frequently used for islet transplantation. The standard preservation method cold storage (CS) inadequately prevents ischemia prior to islet isolation. In kidneys and livers, hypothermic machine perfusion (HMP) is demonstrated to be superior to CS in experimental models and clinical settings. It is hypothesized that HMP improves the quality of pancreata for islet isolation.

Methods:
Human donor pancreata unsuitable for clinical transplantation were connected to our modified dual arterial machine perfusion system, after an initial period of cold ischemia during transport. Islets were isolated after 6 hours of oxygenated HMP. The islet equivalent (IEQ) was analyzed at day 0 and day 3. In vitro islet function was analyzed by performing a dynamic glucose stimulated insulin secretion (GSIS) test. After 3 or 4 days of culture, islets were transplanted under the kidney capsule in STZ-induced diabetic mice (3000 IEQ/mouse). Blood glucose levels were monitored every other day for 28 days. The results were compared with a control group consisting of CS preserved pancreata which were initially accepted for clinical transplantation.

Results:
So far, 6 pancreata have been included in this study: 3 pancreata from donation after circulatory death (DCD) donors have been subjected to HMP and 3 pancreata from donation after brain death (DBD) donors were included in the CS control group. In the HMP group, islet IEQ after isolation was 336.956 ± 91.019 and declined to 281.521 ± 116.745 after three days of culturing. In the CS group, IEQ declined from 381.340 ± 369.845 to 209.239 ± 154.580 at day 3. Dynamic GSIS showed no difference of in vitro islet function between the groups. After transplantation in mice, HMP preserved islets were able to achieve normoglycemia in more mice than the CS preserved islets. Because of high variability, no significant differences between groups were seen.

Conclusion:
The preliminary data suggests that functional, viable islets can be readily isolated from pancreata after HMP. Inclusion of additional pancreata in both HMP group and the CS control group is ongoing.