Clinical aspects and perspectives in islet xenotransplantation

In 1990-1993, eight diabetic renal transplant patients had porcine fetal islets injected intraportally at Huddinge Hospital in Stockholm. Four of the patients had evidence of xenograft function reflected in the excretion of small amounts of porcine C-peptide. Two patients had the porcine fetal islets placed under the capsule of a simultaneously transplanted kidney. In one of these patients, a graft biopsy specimen taken 3 weeks after transplantation revealed morphologically intact epithelial cells staining positively for insulin and glucagon. The insulin production was in all instances insufficient to affect the patient's insulin requirements. All patients formed specific xenoantibodies (mostly anti-Gal); presumably, most of the xenoislets were destroyed by rejection. On follow-up studies carried out 6-8 years after xenotransplantation, most patients still had higher-than-pretransplant levels of xenoantibodies. There was no evidence of transmission of porcine endogeneous retroviruses to the patients. All patients expressed a positive attitude toward the use of animal tissue for treatment of disease, and none of the patients regretted participating in the trial. Cell transplantation is leading the way at present for clinical xenotransplantation. The finding that complement inhibition protects intraportally injected porcine islets from an injurious incompatibility reaction holds promise for future clinical application. A similar protective effect might be achievable with the use of islets from transgenic pigs expressing human complement receptors.