Parathyroid xenotransplantation without immunosuppression in experimental hypoparathyroidism: Long-term in vivo function following microencapsulationwith a clinically suitable alginate

Permanent hypoparthyroidism is one of the most difficult of all endocrine d isorders to treat medically. Because this deficiency syndrome rarely is a l ife-threatening condition, systemic immunosuppression for recipients of tra nsgenic transplants is not justified, An alternative would be protecting th e tissue to be transplanted from the immunologic response (immunoisolation) by coating it with a semipermeable membrane-microencapsulation. Unfortunat ely, prior to the first clinical use, further analysis of the coating subst ance (alginate) demonstrated that it has potential cancerogenic properties. Using a purified amitogenic alginate suitable for clinical use, we accompl ished allotransplantation in a longterm animal model and reported the first clinical cases without postoperative immunosuppression recently. In view o f the potential clinical use, we investigated the ability of the microencap sulation technology with the novel amitogenic alginate in experimental hypo parathyroidism (80 parathyroidectomized rats) to enable transgenic transpla ntation across the highest immunologic barrier (xenotransplantation: human to rat) to ensure intact transplant function without immunosuppression, In a controlled, long-term animal study, the effect of microencapsulation on x enotransplanted human parathyroid tissue was evaluated over a period of 30 weeks (microencapsulated and naked hyperplastic parathyroid tissue, respect ively). Functionally, human parathyroid tissue was able to replace that of rats. More than 6 months after xenotransplantation 32 of 40 animals that ha d received microencapsulated transplants were normocalcemic, In contrast, s erum calcium concentrations dropped to postparathyroidectomy levels within 3 weeks in the animals that had received naked tissue only. Correspondingly , normocalcemic animals showed vital parathyroid tissue inside the microcap sules, which were surrounded by a small rim of fibroblasts. When combining microencapsulation with an improved tissue culture method, xenotransplantat ion of human parathyroid tissue and maintenance of its physiologic function is reproducibly achieved over the highest transplantation barrier. Using t he amitogenic alginate may be a crucial step toward the first clinical use of this technique for parathyroid xenotransplantation without immunosuppres sion.