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Tissue Factor and CCL2/Monocyte Chemoattractant Protein-1 Released by Human Islets Affect Islet Engraftment in Type 1 Diabetic Recipients

Department of Medicine (F.B., S.M., P.M., R.M., F.D.T., V.V., A.S.), Unit of Immunology of Diabetes (L.P., E.B.), Coagulation Service and Thrombosis Research Unit (A.D.), and Surgical Department (V.D.C.), Vita-Salute University San Raffaele Scientific Institute, 20132 Milan, Italy

Address all correspondence and requests for reprints to: Federico Bertuzzi, Unit of Cell Therapy for Type 1 Diabetes, S. Raffaele Scientific Institute, Via Olgettina 60, 20132 Milano, Italy. E-mail: bertuzzi.federico{at}hsr.it.

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.

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