MICROENCAPSULATED ISLET XENOGRAFTS IN NOD MICE

DESCRIPTION: (Adapted from investigator's abstract) Microencapsulation of pancreatic islets is proposed as a safe and effective method for long term immunoisolation. Rodent transplants in microcapsules have reversed diabetes in rodents for greater than one year. However, in order to consider large animal transplants, two problems need to be addressed. First, animals larger than rodents do not react to the microcapsules similarly to rodents; i.e., the presence of a foreign body reaction limits the function of the graft. Second, inasmuch as a ratio of one donor to one recipient has not been achieved for pancreatic islet grafts, an effective mass isolation technique for large animals is necessary. The first specific aim of this research is to further refine a technically simple isolation technique designed for processing large amounts of tissue; specifically, human and porcine. Preliminary work demonstrates it is at least as effective as the current techniques of the literature and technically easier. The applicants' supply of human pancreata is generated through the cooperation of the Greater New York Regional Transplant Program. Adult pigs are sacrificed in the Institute of Comparative Medicine facilities of Columbia Presbyterian Medical Center. The second specific aim is to further elucidate and refine the technology of microencapsulation. Large animal data reveal that modifications of the polyelectrolyte membrane are essential to long term success. Several substitutions of currently used reagents are under preliminary investigation; e.g., substituting the acidic polysaccharide heparin for dilute alginate. Also, the highly ionic bonding of the membrane may allow incorporation of more weakly charged moieties in its inner layers; e.g., angiostatic steroids. This represents the most difficult but potentially the most rewarding aspect.