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Pancreatic islet transplantation: isolation, separation, and microvascularization.

Twenty years ago Ballinger and Lacy were the first to report cure of experimental diabetes in rats after free transplantation of isolated pancreatic islets. In a remarkable number of experimental studies on transplantation of isolated islets of Langerhans reversal of diabetes and restoration of normal glucose metabolism has been achieved in rodents. However, studies in larger animals and clinical attempts have been less successful. Beside graft rejection, the isolation and purification of a sufficient mass of islets have been identified as major obstacles. In addition, insufficient revascularization is thought to be, in part, responsible for early graft failure. Recent developments allow for consistently high yields of isolated islets using an automated method, in particular for isolation of human pancreatic islets. Furthermore, a variety of techniques have been implemented during the past years improving purification, including gradient separation, fluorescence-activated sorting, magnetic microsphere extraction and cryopreservation. Revascularization of the islet grafts may be enhanced by selection of adequate sites for transplantation and/or by supportive application of angiogenic peptides. Progress achieved during the past years allow for new hope for successful clinical islet transplantation.