Identification of in vitro parameters predictive of graft function: a study in an animal model of islet transplantation

• Published in: Transplantation proceedings Vol. 36; no. 3; pp. 612 - 613
• Main Authors: Migliavacca, B, Nano, R, Antonioli, B, Marzorati, S, Davalli, A.M, Di Carlo, V, Bertuzzi, F
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.04.2004; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Blood Glucose; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - surgery; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Ethanol - analogs & derivatives; Graft Survival - physiology; Humans; Islets of Langerhans Transplantation - methods; Management. Various non-drug treatments. Langerhans islet grafts; Medical sciences; Mice; Mice, Nude; Models, Animal; Predictive Value of Tests; Subrenal Capsule Assay; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Transplantation, Heterologous; Animal model; Langerhans islet; Homograft; Model study; Identification; Transplantation; In vitro; Treatment; Animal; Surgery; Graft; Predictive factor; Endocrine pancreas
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2004.03.073

The quality of human islets is one of the factors decisive for the success of human islet transplantation. Several parameters have been proposed to characterize islet quality, but none of them has been able to predict the fate of a transplant. The aim of our study was to correlate a panel of in vitro parameters for islet viability with their in vivo function after transplantation in nude mice. Islets were obtained after enzymatic digestion of a human pancreas; they were purified from exocrine tissue using a continuous-density gradient. Two aliquots of islets (1000 and 2000 islets) were transplanted under the kidney capsule of diabetic nude mice. The animals were followed for 1 month with repeated measurements of blood glucose and body weight. One month after transplantation, mice were killed and their graft harvested for histologic analysis. In parallel we studied in vitro islet viability with propidium iodide and fura-2, their insulin content, their purity, and their insulin response to glucose upon static incubation. Ten islet preparations were transplanted: 3 out of 10 preparations did not restore normoglycemia; 4 out of 10 normalized glycemia only in mice receiving 2000 islets, and 3 out of 10 fully restore normoglycemia in all mice. The purity of preparations (R2 = 0.63 and 0.85, respectively, with 1000 and 2000 islets) and the insulin content (R2 = 0.75 with 2000 IE) correlated with transplant success. These data show that purity of islet preparations and their insulin content should be useful parameters for the selection of islet preparations for transplant purposes.