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Biomedical subjects

Simona Marzorati

Publications and source records attributed to Simona Marzorati.

3 recordsLinked to original sources

Islet cell transplantation.

Islet cell transplantation is an attractive alternative therapy to conventional insulin treatment or vascularized whole pancreas transplantation for type 1 diabetic patients. It represents a successful example of somatic cell therapy in humans based on complex procedures for islet isolation from whole pancreas. The islets, that are only 1% of the total pancreas tissue, are isolated by two steps method starting with collagenase digestion that operates a rapid dissociation of the stromal component of the gland, while preserving islet anatomical integrity. After digestion, islets are then separated from exocrine tissue by centrifugation in density gradients. Transplantation consists of a simple injection of few milliliter-purified tissue in the portal vein through a percutaneous trans-hepatic approach performed in local anesthesia. Several studies have now demonstrated that islet transplant can replace pancreatic endocrine function without major side effects and with liver viability preservation in selected patients affected by long-term type 1 diabetes. It can restore endogenous insulin secretion, achieve insulin independence in more than 80% of patients, and recover the metabolism of glucose, protein and lipids. Improved control of glycated HbA1c, reduced risk of recurrent hypoglycemia and of diabetic complications are also seen as important benefits of islet cell transplantation, irrespective of the status of insulin independence. Many protocols are now on going for reduction of immunosuppression therapy in recipients, induction of tolerance, and prolongation of graft function.

Animals↗

Donor and isolation variables associated with human islet monocyte chemoattractant protein-1 release.

Human islets have chemotactic activity toward macrophages mediated by the secretion of monocyte chemoattractant protein-1 (CCL2/MCP-1) that negatively affect clinical outcome in islet after kidney recipients. The aim of the present work was to identify the donor features and the variables involved in the procedures of islet isolation associated with islet CCL2/MCP-1 release in vitro. We used a retrospective approach studying the outcome in 170 islet isolations. The univariate analysis demonstrated that CCL2/MCP-1 release was significantly associated with the surgical team in charge for organ harvesting, the proteins for dilution solution, the type of gradient, the type of enzyme, and the donor noradrenalin treatment. The multivariate analysis confirmed that the surgical team (P = 0.001) and the enzyme (P = 0.001) were independently associated with in vitro CCL2/MCP-1 islet release (r(2) = 17%). Strategies aimed to optimize the procedures of organ harvesting and islet isolation may reduce the pro-inflammatory properties of the preparation and therefore may improve islet engraftment.

Chemokine CCL2↗

Tissue factor and CCL2/monocyte chemoattractant protein-1 released by human islets affect islet engraftment in type 1 diabetic recipients.

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) (r(2)=0.26, P = 0.001) and CCL2/MCP-1/EI (r(2) = 0.42; P < 0.001); serum transaminase areas under the curve in the first week posttransplantation were correlated with CCL2/MCP-1/EI (r(2) = 0.55; P < 0.001 for ALT and r(2) = 0.51; P = 0.001 for AST) and TF/EI (r(2) = 0.31; P = 0.002 for ALT, and r(2) = 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.

Chemokine CCL2↗