The efficacy of an immunoisolating membrane system for islet xenotransplantation in minipigs.

Developing a device that protects xenogeneic islets to allow treatment and potentially cure of diabetes in large mammals has been a major challenge in the past decade. Using xenogeneic islets for transplantation is required in light of donor shortage and the large number of diabetic patients that qualify for islet transplantation. Until now, however, host immunoreactivity against the xenogeneic graft has been a major drawback for the use of porcine islets. Our study demonstrates the applicability of a novel immunoprotective membrane that allows successful xenotransplantation of rat islets in diabetic minipigs without immunosuppressive therapy. Rat pancreatic islets were encapsulated in highly purified alginate and integrated into a plastic macrochamber covered by a poly-membrane for subcutaneous transplantation. Diabetic Sinclair pigs were transplanted and followed for up to 90 days. We demonstrated a persistent graft function and restoration of normoglycemia without the need for immunosuppressive therapy. This concept could potentially offer an attractive strategy for a more widespread islet replacement therapy that would restore endogenous insulin secretion in diabetic patients without the need for immunosuppressive drugs and may even open up an avenue for safe utilization of xenogeneic islet donors.

Neutrophil adhesion molecule expression in familial Mediterranean fever: discordance between the intravascular regulation of beta2 integrin and L-selectin expression in acute attack.

BACKGROUND: To determine the surface expression of neutrophil beta2 integrin (CD11b/CD18) and L-selectin (LS) adhesion molecules in patients with familial Mediterranean fever (FMF) and to investigate the in vitro regulation of their expression in response to chemoattractant stimuli. METHODS: Neutrophil surface expression of CD11b and LS molecules was analyzed by flow cytometry in anticoagulated whole blood drawn from FMF patients and normal controls, and the in vitro regulation of these molecules induced by the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP) was assayed. RESULTS: Patients during acute FMF attacks showed a statistically significant increased neutrophil surface CD11b compared with normal controls (mean fluorescence intensity: 22.8 +/- 13.7 vs 12.8 +/- 10.41, respectively; p = .03). There was no difference in LS expression between the groups. Neutrophils of FMF patients regulate CD11b and LS expression induced by chemoattractant (FMLP) stimulation to a degree similar to that in controls. CONCLUSIONS: beta2 Integrin is up-regulated during an acute attack of FMF in dissociation with LS expression, suggesting a unique nonchemoattractant-mediated neutrophil activation.

Constitutively increased neutrophil surface expression of beta2-integrin in Yemenite Jews.

The aim of this study was to analyze surface expression of neutrophil adhesion molecules in Yemenite Jews as compared to other ethnic populations in Israel. The constitutive neutrophil expression of CD11b and L-selectin (LS), as well as their expression in response to an in vitro chemoattractant and growth factor stimulation were studied by flow cytometry. Mean surface expression of CD11b molecule was statistically significantly increased among the Yemenite Jews tested compared to the non-Yemenite Jews (327.1 +/- 129.2 vs. 237.0 +/- 133.1; p = 0.002), with no significant correlation to their absolute neutrophil count. LS expression was similar in the two study groups. In vitro analysis of CD11b and LS expression induced by chemoattractant and G-CSF showed no difference between neutrophils of Yemenite versus non-Yemenite Jews. The study results suggest that in Yemenite Jews, circulating neutrophils display significantly increased expression of beta2-integrin molecules on their surface compared to non-Yemenite Jews.