FIRST SUCCESSFUL XENOTRANSPLANTATION OF MICROENCAPSULATED HUMAN PARATHYROID TISSUE IN EXPERIMENTAL HYPOPARATHYROIDISM - LONG-TERM FUNCTION WITHOUT IMMUNOSUPPRESSION

Owing to the complexity of the parathyroid hormone's metabolic interac tions, clinical hypoparathyroidism is one of the most difficult of all endocrine disorders to treat. Therefore, causative treatment of this disorder by transplantation of parathyroid glands is highly desirable. We have recently documented the long-term in vivo function of iso- an d allotransplanted rat parathyroid tissue without systemic immunosuppr ession in an animal model. In view of the potential clinical use of th is method, human parathyroid tissue has been microencapsulated and tra nsplanted over the highest immunological barrier. In a controlled, lon g-term animal study in the parathyroidectomized rat, the effect of mic roencapsulation on xenotransplanted human parathyoid tissue was evalua ted over 30 weeks (native and microencapsulated parathyroid tissue = 4 0 rats respectively). Functionally, human parathyroid tissue was able to replace that of the rat. All animals that had received microencapsu lated parathyroid tissue were normocalcemic for 16 weeks; 27/40 at the end of the study. In contrast, serum calcium concentrations dropped t o post-parathyroidectomy levels within 4 weeks in those animals that h ad received native tissue only. Histologic evaluation of the explanted , functionally successful xenografts showed vital parathyroid tissue i nside intact microcapsules surrounded by a small rim of fibroblasts. A vital fibrotic remnants were demonstrated in animals with non-encapsul ated parathyroid tissue. Thus, we have established the feasibility of microencapsulation of human parathyroid tissue, preserving its viabili ty over long periods in vivo even if xenotransplanted. In combination with an improved tissue culture method, transplantation of human parat hyroid tissue and maintenance of its physiological function is reprodu cibly achieved without postoperative systemic immunosuppression over t he highest transplantation barrier. This may be a crucial step towards the first clinical application of this method.