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Islet cell transplantation as a cure for insulin dependent diabetes: current improvements in preserving islet cell mass and function

MagaliJ.Fontaine

   OBJECTIVE: To review the current progress of islet cell transplantation in patients withinsulin-dependent diabetes, emphasizing on the difficulties with recovering and preserving islet cellmass and function, 30% of which is lost during the peri-transplantation period.RESULTS: The islet-cell isolation technique is perfected, but improvements are still progressing in twomajor directions: preservation of islet cells and tolerance induction. Optimum islet cell viability andfunction depends on appropriate revascularization of the islet graft and blockade of thrombus formation aswell as cytokine and free radical release. Conditioning the islet cells in-vitro prior to transplantation toeither upregulate VEGF expression or downregulate NF-kappa B transcription factor has proven to improverevascularization and to prevent islet cell apoptosis and cytokine-mediated damage. Tolerance induction iscurrently being best achieved by selecting and combining immunosuppressive agents such as monoclonalantibodies which target the major signaling molecules during immune activation, but which are least toxicto islet cells.CONCLUSIONS: Patients with insulin-dependent diabetes will greatly benefit from current developmentsin effective approaches to protect islets during the peritransplant period. Emerging interest in stem cellbiology and differentiation may provide the ultimate solution to the problem of organ scarcity and isletcell protection from the peritransplant induced damage.……