Could pancreatic islets derived from pancreases from NHB-III donors be used as autonomous single islet grafts?

M.A. Engelse¹, C.J.M. Loomans¹, E.H. van Rossenberg¹, H.A.M. Tons¹, C. Vermeulen¹, J. Ringers², A. Braat², A. Baranski², J. Dubbeld², S. Schaapherder², R. Ploeg³, E.J.P, de Koning^1
1 Leiden University Medical Center, Dept. of Nephrology, Leiden, The Netherlands; ² Leiden University Medical Center, Dept. of Surgery, Leiden, The Netherlands; ³ University Medical Center Groningen, Dept. of Surgery, Groningen, The Netherlands

Isolation of pancreatic islets is worldwide performed on organs that are obtained from heartbeating (HB) organ procurement procedures. Distinctively, in the Netherlands and in Belgium a strong tradition has developed in the acquisition of high quality pancreas from (Non-HeartBeatingtype-III) NHB-III donors. In this study, the feasibility of using pancreatic islets from high quality NHB-III donors autonomously is investigated. First, pancreatic islets from both NHB-III (n=3) and HB (n=23) procedures were isolated using the same isolation method. We determined the total islet number, their viability and their ability to produce insulin in response to an elevated glucose stimulus (GIIST). In a second experiment, we acquired NHB-III(n=2) and HB(n=4) human pancreatic islets and performed islet transplantations under the kidney capsule (3000 islet equivalents per mouse) of streptozotocin (STZ)-treated (diabetic) NOD-SCID mice. In the first experimental group, the number of pancreatic islets derived from NHB-III (519.300 ± 207.500 IEQ) and HB ( 502.900 ± 307.000 IEQ) donors did not differ significantly. The stimulation index (GIIST) was similar as well for islets obtained from NHB-III (5.8x) and HB(6.3x) donors. In the second experimental group, islets derived from NHB-III donors were demonstrated to have a slight tendencyto be less effective at alleviating STZ-induced hyperglycaemia at 30 days after transplantation: 12,38±0,7mM(NHB-III) vs 8,2±6,3mM(HB) fasting glucose levels,though this variation was not significant. Pancreas from NHB-III donor procedures are a good potential source for pancreatic islet isolation and subsequent islet transplantation. Our studies demonstrate no appreciable differences in yield or function between NHB-III and the commonly-used HB pancreas. However, we stress that only the best pancreas from NHB-III donors are used that had a patent perfusion prior to procurement. In conclusion, we propose the application of islets from NHB-III for autonomous transplantation.