European Society for Organ Transplantation (ESOT) Consensus Statement on the Role of Pancreas Machine Perfusion to Increase the Donor Pool for Beta Cell Replacement Therapy

The advent of Machine Perfusion (MP) as a superior form of preservation and assessment for cold storage of both high-risk kidney’s and the liver presents opportunities in the field of beta-cell replacement. It is yet unknown whether such techniques, when applied to the pancreas, can increase the pool of suitable donor organs as well as ameliorating the effects of ischemia incurred during the retrieval process. Recent experimental models of pancreatic MP appear promising. Applications of MP to the pancreas, needs refinement regarding perfusion protocols and organ viability assessment criteria. To address the “Role of pancreas machine perfusion to increase the donor pool for beta cell replacement,” the European Society for Organ Transplantation (ESOT) assembled a dedicated working group comprising of experts to review literature pertaining to the role of MP as a method of improving donor pancreas quality as well as quantity available for transplant, and to develop guidelines founded on evidence-based reviews in experimental and clinical settings. These were subsequently refined during the Consensus Conference when this took place in Prague.</p

Successful pancreas allotransplantations after hypothermic machine perfusion in a novel diabetic porcine model: a controlled study

International audienceThe standard technique for pancreas preservation for transplantation is static cold storage (SCS). In this experimental study, we compare SCS to hypothermic machine perfusion (HMP) of the pancreas to assess if the latter could safely prolong the ischaemia period prior to transplantation. We worked in two phases, first with organ preservation for 24 h and second, preservation for either 2 or 6 h before allotransplantation. In phase 1, exocrine injury markers were found to be nonsignificantly lower, in the HMP group (n = 3) vs. SCS (n = 3) after 24 h of preservation; amylase (P = 0.2), lipase (P = 0.3) and lactate dehydrogenase (P = 0.1). In phase 2, 14 recipient diabetic pigs (after total pancreatectomy) received allotransplantations with n = 4 and n = 4 pancreases after HMP for 2 and 6 h vs. n = 3 and n = 3 pancreases after SCS for 2 and 6 h, respectively. There were no differences in recipient survival (P = 0.7), and mean survival was 14 days (0-53 days). All recipients had allograft function defined as detectable C-peptide and independent normoglycemia. We have not highlighted vascular thrombosis in all allotransplantations. This study reports the first successful pancreas allotransplantation after HMP preservation for up to 6 h with no evidence of graft thrombosis

Total Pancreatectomy and Pancreatic Allotransplant in a Porcine Experimental Model

International audienceObjectives: The main objective of this experimental study was to evaluate the feasibility of diabetes induction by total pancreatectomy and pancreatic allotransplant after diabetes induction by total pancreatectomy. The secondary objective was to evaluate metabolic (C-peptide, glycemia) and inflammatory (lactate and platelet levels) parameters after diabetes induction by total pancreatectomy and pancreatic allotransplant after total pancreatectomy. Materials and Methods: The study protocol wasapproved by the French Minister of Research (APAFiS no.18169). Insulin-dependent diabetes was induced bytotal pancreatectomy in one male Susscrofa pig, and pancreatic allotransplant was performed, after total pancreatectomy, in 3 male Susscrofa pigs. Total pancreatectomy was performed under general anesthesia, with meticulous dissection of the portal veinand the splenic vein to preserve the spleen. Concerning pancreas procurement, extensive pancreas preparation occurred during the warm phase, before cold perfusion. Pancreatic allotransplant was performed using donor aorta (with superior mesenteric artery and celiactrunk).Results: Diabetes induction was successful, with negative C-peptide values at 3 hours after total pancreatectomy. Glycemic control without hypoglycemic events was obtained with the use of long-acting insulin administered once per day. No rapid-acting insulin was used. In animals that received pancreatic allotransplant, after enteral feeding was started, glycemic control without hypoglycemic events and without insulin was obtained in 2 animals.Conclusions: In an experimental porcine model, diabetes induction by total pancreatectomy and pancreatic allotransplant after total pancreatectomy are feasible and effective. The development of these models offers the potential for new investigations into ischemia-reperfusion injuries, improvement of pancreas procurement methods, and preservation techniques

Ischemia-Reperfusion Injuries Assessment during Pancreas Preservation

International audienceMaintaining organ viability between donation and transplantation is of critical importance for optimal graft function and survival. To date in pancreas transplantation, static cold storage (SCS) is the most widely practiced method of organ preservation. The first experiments in ex vivo perfusion of the pancreas were performed at the beginning of the 20th century. These perfusions led to organ oedema, hemorrhage, and venous congestion after revascularization. Despite these early hurdles, a number of factors now favor the use of perfusion during preservation: the encouraging results of HMP in kidney transplantation, the development of new perfusion solutions, and the development of organ perfusion machines for the lung, heart, kidneys and liver. This has led to a resurgence of research in machine perfusion for whole organ pancreas preservation. This review highlights the ischemia-reperfusion injuries assessment during ex vivo pancreas perfusion, both for assessment in pre-clinical experimental models as well for future use in the clinic. We evaluated perfusion dynamics, oedema assessment, especially by impedance analysis and MRI, whole organ oxygen consumption, tissue oxygen tension, metabolite concentrations in tissue and perfusate, mitochondrial respiration, cell death, especially by histology, total cell free DNA, caspase activation, and exocrine and endocrine assessment

Development of ex situ normothermic reperfusion as an innovative method to assess pancreases after preservation

International audienceStatic cold storage (SCS) is the standard method for pancreas preservation prior to transplantation; however, it does not permit organ assessment. Normothermic reperfusion (NR) is utilized clinically for other organs to assess viability. Our aim was to develop NR using normothermic machine perfusion technique to simulate reperfusion at the time of transplantation, enabling evaluation of oxygenated hypothermic machine perfusion (HMPO2) as a newer strategy to optimize pancreas preservation. 13 porcine pancreases procured after circulatory death were divided into 3 groups: 4 pancreases preserved using SCS, and 2 groups preserved by HMPO2 (n = 4 and n = 5, differing by type of preservation solution). Duration of perfusion or cold storage was 6 hours before the 1-hour assessment using NR. Outcome measures were perfusion characteristics, biochemistry and change in tissue water mass as oedema assessment. During NR, the HMPO2 groups demonstrated better perfusion characteristics, normal macroscopic appearances, decreased water mass and one HMPO2 group demonstrated a response to glucose stimulation. Conversely, the SCS group showed an increased water mass and developed early macroscopic appearances of oedema, interstitial haemorrhage and minimal portal outflow. This study suggests that ex situ assessment of pancreases by NR is promising, and that HMPO2 may be better than SCS