Parameters favouring successful adult pig islet isolations for xenotransplantation in pig-to-primate models

• Published in: Xenotransplantation (Københaven) 2006-05, Vol.13 (3), p.204-214
• Main Authors: Dufrane, Denis, D'hoore, William, Goebbels, Rose-Marie, Saliez, Alain, Guiot, Yves, Gianello, Pierre
• Format: Article
• Language: English
• Subjects: Adenosine; Allopurinol; Animals; Blood Glucose - metabolism; Cell Separation - methods; Cynomolgus; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - surgery; Glutathione; guidelines; Insulin; islet isolation; Islets of Langerhans - cytology; Islets of Langerhans Transplantation - methods; Islets of Langerhans Transplantation - physiology; Macaca fascicularis; Organ Preservation; Organ Preservation Solutions; Pancreas - cytology; parameters; pig islets; Primates; Raffinose; Regression Analysis; Swine; Transplantation, Heterologous - methods; Transplantation, Heterologous - physiology; Treatment Outcome; xenotransplantation
• ISSN: 0908-665X; 1399-3089
• DOI: 10.1111/j.1399-3089.2006.00275.x

Dufrane D, D'hoore W, Goebbels R‐M, Saliez A, Guiot Y, Gianello P. Parameters favouring successful adult pig islet isolations for xenotransplantation in pig‐to‐primate models.
Xenotransplantation 2006; 13: 204–214. © Blackwell Munksgaard, 2006 :  Background:  In the near future, adult porcine islets of Langerhans appear as an unlimited source of insulin‐producing cells which could play a major role for treating diabetes mellitus. There is, however, an obvious lack of pre‐clinical results and data in the pig‐to‐primate model. One of the main hurdles of this model is certainly related to the difficulty of reproducing regularly successful porcine islet isolation. This experimental work was designed to provide guidelines applicable in pig pancreas procurement and islet isolation for successful islet xenotransplantation into primates. Methods:  Pancreases were harvested from adult Belgium Landrace pigs (n = 79) in a single centre. The impact on islet yield of (1) pancreas procurement (blood exsanguination and warm ischaemia time (WIT)), (2) cold storage solutions (classic UW and modified UW (without hydroxyethyl starch and inverse K+/Na+ concentration)), (3) a dynamic or static method of pancreas digestion, and (4) the endotoxin content and enzymatic activity from five different batches of Liberase PI was studied. In addition, pancreatic biopsies (n = 18), performed before isolation, were retrospectively analyzed to study the impact of histomorphometry on porcine islet yield. Finally, two diabetic cynomolgus monkeys were transplanted without immunosuppression with 15 000 pig islet equivalents/kg body weight of recipient to assess in vivo the function of freshly isolated islets. Univariate and multivariate analyses were performed. Results:  By multiple linear regression, the most significant variables that significantly improved islet yield were, firstly, the presence of