Factors influencing parathyroid allotransplantation in rats

For nearly a century, researchers have sought to solve the problem of permanent hypocalcemia by allotransplanting the parathyroid glands. A thorough review of the literature revealed conflicting reports, many of which claim success but lack substantial data and sound criteria on which to base the success. At the present, there is no reproducible method of successfully transplanting parathyroid tissue to a nonimmunosuppressed host. The literature on the transplantation of other organs was reviewed in order to determine which methods might be tested on parathyroid tissue to achieve long-term graft survival. These methods include the use of fetal tissue and treatment of the host with cyclosporine. Cyclosporine is unique in that it affects graft rejection but does not alter the nonspecific defenses of the host. Five experimental groups were established to study variables influencing successful allotransplantation. Heterogeneic, parathyroid adult rats with calcium levels below 5.5 mg/dl were the graft recipients. Our criteria for successful parathyroid transplantation included biochemical, functional, and histologic data. Maintenance of serum calcium levels above 8.0 mg/dl was considered biochemical evidence of graft function. Excision of the graft site with the subsequent return to pregraft hypocalcemia was considered evidence of graft function. Histologic evidence of normal parathyroid tissue at the graft site was the final criterion used to prove a successful transplant. Graft failure was documented through serum calcium determinations and histologic examination of the graft site. Rats from group 1 received allotransplanted adult parathyroid glands and showed no evidence of graft function. Animals from group 2 received parathyroid allografts from newborn rats and responded with a transient rise in serum calcium levels. Group 3 rats demonstrated a short period of normocalcemia after receiving fetal parathyroid allografts. In addition to undergoing fetal parathyroid allotransplantation, the rats in group 4 were treated with a 7-day course of cyclosporine. Calcium levels rose quickly and remained elevated for 2 weeks after cessation of cyclosporine. Calcium levels then returned to pregraft levels. Group 5 rats received continuous cyclosporine for 40 to 90 days after receiving fetal parathyroid allografts. These animals showed long-term graft survival by biochemical, functional, and histologic analysis.