Leiden University Medical Center
Preliminary results of isolated islets after hypothermic machine perfusion of human donor pancreata
Marjolein M. Leemkuil1, Jason J.B. Doppenberg2, Rutger R.J. Ploeg3, Christina C. Krikke1, Eelco E.J.P. de Koning2, Marten M.A. Engelse2, Henri H.G.D. Leuvenink1.
1Department of surgery, University Medical Center Groningen, Groningen, Netherlands; 2Department of nephrology , Leids University Medical Center, Leiden, Netherlands; 3Transplant surgery, Oxford Transplant Center, Oxford, United Kingdom
Background: Islet transplantation is an effective treatment option for patients with type I diabetes mellitus. Due to the persistent organ shortage, pancreata from marginal donors are more frequently used for islet transplantation. The conventional preservation method cold storage (CS), inadequately prevents ischemia prior to islet isolation. It is hypothesized that hypothermic machine perfusion (HMP) improves the quality of pancreata for islet isolation.
Methods: Human donor pancreata unsuitable for clinical transplantation were connected to our modified dual arterial kidney machine system, after an initial period of cold ischemia during transport. Islets of Langerhans were isolated after six hours of oxygenated HMP. Islet viability was analyzed by fluorescein diacetate (FDA) and propidium iodide (PI) staining. Islet viability was analyzed by performing a glucose stimulated insulin secretion (GSIS) test. After three or four days of culture, the 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.
Results: So far, three DCD pancreases have been included in this study. The preliminary data show an IEQ after isolation of 336957 ± 91019 and an IEQ/gram of 4476 ± 1785. Islet viability at day one was 98% ± 0% and at day three 92.6 % ± 4.6%. Static GSIS at day one showed an induction fold of 2.04 ± 0.42 and at day three 2.57 ± 1.52. After transplantation, normoglycemia was achieved in six out of ten mice. In two out of ten mice, blood glucose levels normalized initially, but the graft function declined 14 days after transplantation. Two out of ten mice were terminated because of postoperative complications and early graft failure.
Conclusion: The preliminary data suggests that functional, viable islets can be readily isolated from pancreata after HMP. Inclusion of additional pancreata in the HMP preserved group and in a CS preserved control group is ongoing.
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|