Microencapsulation of Allogeneic Parathyroid Tissue Succeeds by Delaying Immunization of the Host, not by Protecting the Graft Against the Host’s Activated Immune System*

Background: To examine in an experimental animal study whether alginate microencapsulation of allogeneic parathyroid tissue succeeds by protecting the graft against the host’s activated immune system or by delaying immunization of the host. Methods: Lewis and Dark Agouti rats (n = 200 of each) were used. Parathyroidectomy (PTX) of the hosts was followed by allogeneic transplantation of microencapsulated parathyroid tissue (PT) to the following 3 groups of 5 animals each without immunosuppression: group I, early onset immunoreaction, group II, late onset immunoreaction, and group III, immunization. In group I, an allogeneic skin graft from the same donor was transplanted 3 weeks after microencapsulated PT transplantation and the rejection time determined to assess the host’s immunoreaction. In group II, allogeneic skin graft transplantation was carried out under the identical conditions 8 weeks after microencapsulated PT transplantation. And in group III, allogeneic skin graft transplantation was performed as an immunostimulant 3 weeks before transplantation of microencapsulated PT. Each of the 3 study groups I to III was compared with a corresponding control group I to III receiving native PT allotransplants. Once a week, the titers of cytotoxic antibodies were analyzed and graft function was monitored based on total serum calcium levels [Ca++]. In group IV, 2 allogeneic skin grafts within 2 weeks were given after PTX (study animals), or without prior PTX (controls). Results: Four out of 5 animals in group I, and 3 out of 5 animals in group II lost graft function within 11 weeks after transplantation of microencapsulated PT. In the respective control groups, graft function was lost within 6 weeks. Surprisingly, none of the immunostimulated animals in group III experienced any transplant success, all allogeneic skin grafts being rejected within 11.6 days. There was no significant (p > 0.05) difference in skin graft rejection between study and control groups III. Low cytotoxic antibodies were detected in both study animals and controls of all 4 groups one week after PT allotransplantation (p > 0.05 study and control groups), whereas cytotoxic antibodies were elevated to peak levels in all animals immediately after skin graft transplantation. Conclusion: Earlier successes in microencapsulation technology are not due to the protection offered to the graft by alginate microencapsulation, but rather by the delayed immunization of the host.