METHOD FOR FABRICATION OF COHERENT MICROCAPSULES - A NEW, POTENTIAL IMMUNOISOLATORY BARRIER FOR PANCREATIC-ISLET TRANSPLANTATION

A novel method for immunoprotection of individual, isolated islets, wi thin coherent microcapsules (CM) is described. CM, unlike standard alg inate/polyaminoacidic (AG/PA) microcapsules, whose equatorial diameter ranged from 500 to 800 mu m, were designed so as to conform to the is let surface, thus virtually eliminating any volume-consuming, idle, de ad space. By using a completely new approach for membrane formation, a nd properly adjusting stoichiometric molar ratios of AG/PA;I, we obtai ned a new prototype of CM. Ease and safety of CM fabrication was assoc iated with full preservation of the enveloped islet morphologic integr ity, viability and functional competence, regardless of donor islet sp ecies employed. In vitro CM immunobarrier competence was demonstrated by co-culturing encapsulated rat islets with splenocytes belonging to highly reactive pairs. Subcapsular renal implant of either empty or xe nogeneic islet containing CM, in normal mice, demonstrated membrane bi ocompatibility and in vivo immunobarrier competence, respectively, wit h full retention of the explanted islet viability, in absence of any i nflammatory cell CM overgrowth Finally, intraperitoneal graft of rat i slet containing CM into diabetic mice hesitated in normalization or dr amatic lowering of non-fasting blood glucose (NFBG) of these animals, which to date is being sustained long-term in one recipient.