Transplantation of Allogeneic/Xenogeneic Pancreatic Islets Containing Coherent Microcapsules in Adult Pigs

Abstract

WE HAVE PREVIOUSLY described a method for fabrication of alginate/polyaminoacidic CM. Thereafter, we completed assessment of either morphological properties of structural as well as ultrastructural level, or in vitro immunoselectivity, or in vivo post-transplant (Tx) functional performance in diabetic rodents of these new biomembranes for islet Tx immunoprotection in full absence of the recipient’s pharmacological immunosuppression. Because CM, unlike conventional-size microcapsules (CSM), measuring an average 600 to 800 mm in equatorial diameter, hold the unique advantage of occupying a volume which is almost coincident with that of naked islets, these new microimmunobarriers could address a number of unsolved problems with regard to encapsulated islet cell Tx in diabetic large mammalians. One of the most formidable hurdles to this approach for the therapy of insulin-dependent diabetes mellitus has consisted of inadequacy of implant sites for encapsulated islets. Because of the final excessive CSM’s Tx size, these capsules had been only implanted in the peritoneal cavity. Unfortunately, even if highly biocompatible, intraperitoneally grafted, islet-containing microcapsules had often provoked severe, possibly mass-related (60 to 80 mL/diabetic dog) inflammatory cell reaction. Dense connective tissue infiltration invariably resulted in impairment of biochemical exchange, ultimately leading to Tx failure. After testing the new CM in either in vitro functional and immunological or in vivo rodent diabetes-correction studies, we had embarked on assessment of CM biocompatibility, after multiple-site transplantation into adult pigs. Preliminarily, we have shown that empty CM, per se, indeed were biocompatible in this large-size mammal animal model, with a very low degree of sensitization being induced by repeated CM-Tx booster. In an attempt to determine whether CM, because of their minimal size, would permit access to Tx sites so far interdicted to CSM, including parenchymatous organs, with full retention of the encapsulated allogeneic/xenogeneic islet cell viability, we have transplanted porcine or canine islet containing CM into multiple Tx sites, and examined them histologically, at 30 days post-Tx, in normal, adult pigs. MATERIALS AND METHODS Animals