In vitro modulation of monocyte chemoattractant protein-1 release in human pancreatic islets

• Published in: Transplantation proceedings Vol. 36; no. 3; pp. 607 - 608
• Main Authors: Marzorati, S, Melzi, R, Nano, R, Antonioli, B, Di Carlo, V, Piemonti, L, Bertuzzi, F
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2004; Elsevier Science
• Subjects: Biological and medical sciences; Cell Culture Techniques - methods; Cell Separation - methods; Chemokine CCL2 - secretion; Culture Media; Cytokines - secretion; Diabetes Mellitus, Type 1 - surgery; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Humans; Inflammation - prevention & control; Islets of Langerhans - cytology; Islets of Langerhans - secretion; Islets of Langerhans Transplantation; Macrophages - cytology; Management. Various non-drug treatments. Langerhans islet grafts; Medical sciences; Monocytes - cytology; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Immune response; Treatment; Surgery; Modulation; Langerhans islet; Graft; Transplantation; In vitro; Release; Monocyte chemoattractant protein 1; Endocrine pancreas
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2004.02.048

Islet transplantation is a new approach to treat type 1 diabetic patients. Despite its great potential and progressively increasing success rate, islet engrafment still represents an unsolved problem. Only part of the transplanted β-cell mass survives after infusion due to hypoxia and inflammatory reactions, principally mediated by macrophages. We have demonstrated that human islets release monocyte chemoattractant protein-1 (MCP-1), one of the most powerful macrophage chemokines, which may impair the fate of a transplant. In this study we have attempted to modulate in vitro MCP-1 release by human islets. Human islets isolated using the automated method were cultured in CMRL or M199 standard culture media alone or supplemented with (1) two intracellular kinase inhibitors (10 μmol/L RO8220, a protein kinase C inhibitor, and rcAMP 20 μmol/L, a protein kinase A inhibitor) or (2) two antioxidant and cell-protective agents (vitamin E, vitamin B); or (3) immunosuppressive drugs (0.001 to 10 ng/mL cyclosporine, 0.1 to 100 ng/mL rapamycin, 0.1 to 10 ng/mL tacrolimus, 0.001 to 10 ng/mL mycophenolate acid). We observed that the only culture condition that significantly decreased MCP-1 in human islets were CMRL (31 ± 12 in CMRL vs 539 ± 184 pg/mL, in M199, P < .05) or cyclosporine (514 ± 83 pg/mL in control islet vs 307 ± 13, 231 ± 44, 192 ± 4, 242 ± 113, 169 ± 15 pg/mL in islet plus cyclosporine ranging from 0.001 to 10 ng/mL, respectively, P > .05). The capacity of in vitro factors to decrease human islet MCP-1 release suggests strategies to increase the success of islet transplantation.