Strategies to improve outcome after pancreas and islet transplantation

Currently, the only curative treatment option for patients with diabetes mellitus type 1 is the transplantation of beta cells, by either whole pancreas transplant or transplantation of the isolated islets of Langerhans. Despite the worldwide increase of DM1 patients, there is a decrease in the number of pancreas and islet transplantations. This might be related to the decrease of the number of ‘ideal pancreatic donors’: a brain dead donor, ≤45 years old with a BMI of ≤ 30 kg/m2. In addition, there is reluctance to accept a donor pancreas from donors after circulatory death (DCD), because of the alleged higher risks associated with these organs. This thesis describes the safe utility of these organs when other unfavorable donor characteristics are minimized.
Previous studies have shown that the quality of especially marginal donor kidneys and livers can be improved by hypothermic machine perfusion. This thesis describes the development of a prototype perfusion system for the human pancreas. In a feasibility study, the viability of the pancreatic tissue after hypothermic machine perfusion was found to be significantly higher compared to static cold storage, the current preservation method. After six hours of machine perfusion, viable and well-functioning islets of Langerhans could be isolated and successfully transplanted in diabetic mice.
By changing the acceptance criteria and the use of hypothermic machine perfusion, the number of pancreas and islet transplantation might be expanded within the current donor pool.