Islet transplantation as treatment of type 1 diabetes: from experimental beginnings to clinical application

Experimental islet transplantation started more than 30 years ago when it w as discovered that isolation of the islets of Langerhans from the exocrine tissue of the pancreas was possible with collagenase. In numerous studies o ver the following years in rodents it was shown that transplantation of a s ufficient number of islets into the liver via the portal vein shortly after diabetes induction of the recipient resulted in normoglycemia, aglycosuria , nor mal body weight and the typical diabetic late complications were prev ented. However, those results were limited for the syngeneic system, when a llogeneic islets were transplanted rejection occured within a few days. Imm unosupressive regimen showed only limited success in rodents while immunoal teration procedures (culture at low temperatures, W light irradiation, cryo preservation etc.) were capable to prolong the survival of islets up to 200 days. In contrast to the rodent model in larger animals as pigs, dogs and monkeys immunosuppressive drugs (single and in combination) resulted in mar ked prolongation of allograft survival while immunoalteration of islets wit h those animals was less successful. Because a broader use of islet transpl antation in man will lead to shortage of donor organs xenotransplantation m ay be possibly a solution which is briefly mentioned. - Finally, new strate gies regarding the production of human insulin producing cells for transpla ntation purposes are discussed. - In summary, experimental islet transplant ation has paved the way for using this treatment in human patients.