Growth and function of human parathyroid tissue transplanted to athymic mice

Abstract

The morphology, cell proliferation and function of transplanted normal, hyperplastic and adenomatous human parathyroid tissue was studied after transplantation to athymic mice. The iPTH was evaluated in relation to morphology. Human parathyroid tissue collected during surgery for hyperparathyroidism was implanted subcutaneously into athymic mice (nu/nu-BALB/cA) and was analysed 1, 4, 7 and 12 weeks after transplantation. The transplants were examined by light and electron microscopy and by autoradiography after continuous infusion of 3H-thymidine. The relative amount of viable tissue was evaluated using a computer image analysing programme. Graft function was evaluated by measuring human iPTH in mouse serum. A transplant take ratio of 93% was observed. The proliferation rate in adenoma grafts at 12 weeks after transplantation was five and fifteen times that observed in normal and hyperplastic transplants, respectively. In normal and adenoma groups, a continuous increase in iPTH concentrations was observed, but in the hyperplastic group the iPTH remained on the same level. The secretion of iPTH in relation to the amount of transplanted tissue and the fraction of viable tissue was at the same level at 12 weeks in normal and adenomatous grafted animals. In conclusion, human parathyroid tissue was successfully transplanted and maintained its original structure. The growth potential, but not the iPTH secretion, was significantly higher in adenoma grafts compared to grafts from hyperplastic and normal glands.

A New Animal Model to Assess Angiogenesis and Endocrine Function of Parathyroid Heterografts In Vivo

“…Parathyroid transplant size was maintained over the complete observation time, which is in line with former findings after transplantation of hyperplastic parathyroid tissue (13). In contrast, areas occupied by control grafts dilated during the first week of observation, probably because of pretreatment-induced loss of intercellular coherence.…”

“…We thus deliberately omitted adenomatous tissue reported to exhibit higher growth potential in nude mice (13). Because a skinfold cham- ber model allows detailed analysis of functional microvasculature in awake animals, it is often considered to be the gold standard for in vivo assessment of early angiogenesis (21).…”

“…Transplantation of human parathyroid tissue into nude mice allows exact determination of graft function by species-specific immunoassays (11)(12)(13). It is interesting that iPTH human levels were measured in all animals on day 5 when first ingrowing microvessels were only observed in two of those animals, thus preceding the angiogenic switch.…”

“…Species-specific immunoassay alters transplantation of human parathyroid tissue into nude mice allows the exact determination of graft-derived hormone production and growth-factor expression (11)(12)(13). So far, analysis of angiogenesis has only been performed nondynamically by means of histology after sacrifice of time-matched animals.…”

Inverse relation between mRNA synthesis and secretion of parathyroid hormone in athymic mice grafted with human parathyroid tissueNote

“…In a previous study, parathyroid hormone (PTH) secretion showed an increase during the first 7 weeks after transplantation of human PT tissue to athymic mice. Simultaneously, parenchymal cells multi-plyed and transplants were neovascularised by proliferating and migrating endothelial cells (3,4). It was, however, also found that the transplants showed varying degrees of cell disintegration (3).…”