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

 

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Summary:

Experimental islet transplantation started more than 30 years ago when it was discovered that isolation of the islets of Langerhans from the exocrine tissue of the pancreas was possible with collagenase. In numerous studies over the following years in rodents it was shown that transplantation of a sufficient number of islets into the liver via the portal vein shortly after diabetes induction of the recipient resulted in normoglycemia, aglycosuria, normal body weight and the typical diabetic late complications were prevented. However, those results were limited for the syngeneic system, when allogeneic islets were transplanted rejection occured within a few days. Immunosupressive regimen showed only limited success in rodents while immunoalteration procedures (culture at low temperatures, UV light irradiation, cryopreservation 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 marked prolongation of allograft survival while immunoalteration of islets with those animals was less successful. Because a broader use of islet transplantation in man will lead to shortage of donor organs xenotransplantation may be possibly a solution which is briefly mentioned. - Finally, new strategies regarding the production of human insulin producing cells for transplantation purposes are discussed. - In summary, experimental islet transplantation has paved the way for using this treatment in human patients.