Immunoprotection of human islet grafts in alginate/polyornithine microcapsules: preliminary results

Recent results of the Immunotolerance Network (ITN) multicenter clinical trial on human islet allografts into totally immunosuppressed patients with type 1, insulin-dependent diabetes mellitus (T1DM), have clearly shown limits of this approach for the potential cure of this metabolic disorder ((Shapiro AM, 2006). In fact less than 8% of the transplanted recipient could enjoy remission of hyperglycemia and insulin independency at 5 years post-transplant. If causes for this long-term failure associated with human islet allografts are still being under scrutiny, it is increasingly evident that total immunosuppressive regimen therapy to prevent graft rejection will result in severe damage at level of several organs, including the islet graft itself. Hence new approaches to avoid recipient’s imunosuppression clearly are necessary. During the last years important advances have been made in the knowledge of the characteristics and requirements capsules have to meet in order to provide optimal biocompatibility and survival of the enveloped tissue. Novel insight shows that not only the capsules material but also the enveloped cells should be hold responsible for loss of a significant portion of the immunoisolated cells and, thus, failure of the grafts on the long term. We have developed for the last two decades alginate (AG)-based microcapsules that by enveloping each individual islet would prevent the islet graft-directed immune destruction. Ultra-purification of alginates by methods developed in our laboratory, in association with a unique poly-aminoacidic cation coating, based on poly-L-ornithine (PLO), have progressively made the finite capsule product an extremely biocompatible and selective permeable membrane which effectively turns down the islet cell graft-directed immunity with no need for the recipients’ general immunosuppression.