Xenotransplantation of Microencapsulated Parathyroid Cells as a Potential Treatment for Autoimmune-Related Hypoparathyroidism.

Abstract

Hypoparathyroidism occurs as a part of a complex autoimmune syndrome or iatrogenically after neck surgery. The disease presents many challenges, such as hypocalcemia, hyperphosphatemia, and low/undetectable parathormone levels. Allotransplantation of parathyroid tissue or cells has been reported as a promising option to overcome these effects. Transplantation of microencapsulated parathyroid tissue or cells offers an immune escape, which particularly restores the parathyroid function for autoimmune-related hypoparathyroidism. So far, clinical and in vivo studies have demonstrated limited graft survival and instability for the available biocompatible materials. In addition, the transplant site, proper local isolation, and biocompatibility of materials are directly related to survival rate. A microencapsulated parathyroid xenotransplant model by using high guluronic acid-containing ultrapure alginate transplanted into rat omentum was tested in vivo for 1 year. After stability of empty microcapsules was ensured, parathyroid cells were microencapsulated and transplanted in rats, with results compared versus rats with naked (nonencapsulated) parathyroid cells (both groups followed for 64 weeks). Rats remained normocalcemic, and preinflammatory cytokine levels showed dramatic changes. Despite a delay posttransplant, parathormone levels increased significantly. All retrieved microencapsules elicited pericapsular fibrotic overgrowth; however, the fibrosis area was shown to be well tolerated. The possible role of accumulation/cell infiltration of immune response remains to be elucidated. In conjunction with this, the use of nonencapsulated parathyroid cells was also positively correlated with survival rates. A similar evaluation using ultrapure alginate materials and omental transplantation may enable the future determination for the long-term effects of correction of parathormone insufficiency in patients with severe hypocalcemic responses and other endocrine diseases.