ORCID Profile
0000-0002-4310-2635
Current Organisation
Nanophoria
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Publisher: Springer Science and Business Media LLC
Date: 14-04-2005
DOI: 10.1007/S00125-005-1725-3
Abstract: Efficient islet isolation is an important prerequisite for successful clinical islet transplantation. Although progressively improved, islet yield and quality are, however, unpredictable and variable and require standardisation. Since 1989 we have processed 437 pancreases using the automated method. The donor characteristics, pancreas procurement, and digestion and purification procedures including a wide enzyme characterisation of these pancreases were analysed and correlated with islet yield and transplant outcome. By univariate analysis, islet yield was significantly associated with donor age (r=0.16 p=0.0009), BMI (r=0.19 p=0.0004), good pancreas condition (p=0.0031) and weight (r=0.15 p=0.0056), total collagenase activity (r=0.22 p=0.0001), adjusted collagenase activity/mg (r=0.18 p=0.0002), collagenase activity/solution volume (r=0.18 p=0.0002) and neutral protease activity/solution volume (r=0.14 p=0.0029). A statistically significant contribution to the variability of islet yield in a multivariate analysis performed on donor variables was found for donor BMI (p=0.0008). In a multivariate analysis performed on pancreas variables a contribution was found for pancreas weight (p=0.0064), and for a multivariate analysis performed on digestion variables we found a contribution for digestion time (p=0.0048) and total collagenase activity (p=0.0001). Twenty-four patients with type 1 diabetes received single islet preparations from single donors. In these patients, multivariate analyses showed that the reduction in insulin requirement was significantly associated with morphological aspects of islets (p=0.0010) and that 1-month C-peptide values were associated with islet purity (p=0.0071). These data provide baseline donor, digestion and purification selection criteria for islet isolation using the automated method and indicate that the morphological aspect may be a clinically relevant measure of islets on which the decision for transplant can be based.
Publisher: The Endocrine Society
Date: 11-2004
DOI: 10.1210/JC.2004-0659
Abstract: Islet survival in the early posttransplantation period is likely to be influenced by inflammatory events in and around islets. Twenty-seven human islet preparations were transplanted by 24 infusions into 14 patients with brittle type 1 diabetes under the Edmonton protocol. Patients were monitored for their coagulation [cross-linked fibrin degradation products (XDPs)] and liver function test [aspartate and alanine aminotransferase (AST and ALT)] as markers of early posttransplant complications, and these were correlated with in vitro islet number, purification, volume, monocyte-chemoattractant protein-1 (CCL2/MCP-1) and tissue factor (TF) islet release. Consistent with activation of coagulation pathways and hepatic damage, serum XDP values increased early after 11 infusions and transaminase after 13 of 24 infusions. TF and CCL2/MCP-1 were detected in supernatants of 21 and 22 islet preparations, respectively. Serum XDP peak values were correlated with TF/equivalent islets (EI) (r2=0.26, P = 0.001) and CCL2/MCP-1/EI (r2 = 0.42 P & 0.001) serum transaminase areas under the curve in the first week posttransplantation were correlated with CCL2/MCP-1/EI (r2 = 0.55 P & 0.001 for ALT and r2 = 0.51 P = 0.001 for AST) and TF/EI (r2 = 0.31 P = 0.002 for ALT, and r2 = 0.36 P = 0.002 for AST). These data suggest that reducing the islet proinflammatory state may be a means to reduce the early posttransplant complications and perhaps improve islet engraftment.
Location: United States of America
No related grants have been discovered for Simona Marzorati.