Beta-5 Score to evaluate pig islet graft function in a primate pre-clinical model


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Abstract

Igarashi Y, D'hoore W, Goebbels R-Marie, Gianello P, Dufrane D. Beta-5 Score to evaluate pig islet graft function in a primate pre-clinical model. Xenotransplantation 2010; 17: 449–459. © 2010 John Wiley & Sons A/S.Background:We developed a composite scoring system to accurately assess pig islet function in pre-clinical primate studies.Methods:Two scoring methods that have been clinically validated in human islet allotransplantation were tested in six non-diabetic and nine streptozotocin (STZ)-induced diabetic primates: (i) SUITO index = [1500 × fasting C-peptide (ng/ml)]/[fasting blood glucose (FBG, mg/dl) − 63] and (ii) CP/G ratio = [fasting C-peptide (ng/ml) × 100]/FBG (mg/dl). Both scores were analysed as a function of the β-cell mass of the native primate pancreas. Next, a proposed β5 score based on FBG values, daily glycosuria, post-prandial glycosuria, polydipsia, and polyuria was validated on the same primates. Ranges of normal and pathologic values for each parameter were assessed during 5 months in non-diabetic and diabetic primates, respectively. Finally, scores were tested on the nine STZ-induced diabetic primates, four of which were transplanted with microencapsulated pig islets and five with macroencapsulated pig islets. All parameters required for each score were measured prior to transplantation and up to 12 weeks post-transplantation. For the CP/G ratio after transplantation, primate C-peptide was replaced by porcine C-peptide.Results:The Suito index was not correlated with the pancreatic β-cell mass in contrast to the CP/G ratio (R2 = 0.17, P = 0.645 vs. R2 = 0.76, P = 0.003; respectively). The internal consistency of the parameters implied by the β5 score was confirmed by a Cronbach's alpha test of 0.97. Diabetes was confirmed by a significant decrease in the CP/G ratio and the β5 score before and after diabetes induction, respectively. After transplantation, a significant correlation was found between the CP/G ratio and the β5 score, which reflected the functionality of pig islet xenografts and diabetes control. In addition, the CP/G ratio and β5 score were correlated with the glycosylated hemoglobin course after transplantation and diabetes correction with macroencapsulated pig islets.Conclusion:The proposed β5 score provides a valid tool to accurately assess islet transplantation in a primate pre-clinical model.

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