Experimental parathyroid transplantation: human parathyroid grafts survived and functioned in mice treated with anti-CD4 monoclonal antibody

Abstract

Permanent hypoparathyroidism is one of the most difficult of all endocrine disorders to treat medically. To examine the possibility that xenotransplantation can be used to treat hypoparathyroidism, human parathyroid tissues were transplanted into mice. Human parathyroid tissue was taken from specimens excised from patients with hyperparathyroidism. Fresh human parathyroid tissue was implanted under kidney capsule of CBA (H2k) mice. Some mice were treated intraperitoneally with depleting anti-CD4 monoclonal antibody (mAb, YTA 3.1, 100 microg/dose, days -1. 0. 1, 2, 3, and 5). Mice were killed 30 days after transplantation. Survival of parathyroid grafts was examined microscopically and human parathyroid hormone in serum was measured by ELISA. All parathyroid grafts survived under kidney capsule and human parathyroid hormone was strongly detected in serum (621 +/- 576 pg/mL) when recipients were treated with short-course treatment of anti-CD4 mAb. Conversely, no parathyroid tissue was seen microscopically in any recipient mice without anti-CD4 mAb treatment. Human parathyroid hormone was undetectable by ELISA in naive mice and mice transplanted with human parathyroid tissue without short-course treatment of anti-CD4 mAb. Xenogeneic human parathyroid tissue survived and functioned in mice treated with short-course treatment of anti-CD4 mAb.