Revascularisation of human parathyroid tissue transplanted to athymic mice

Abstract

The revascularisation process of transplanted human normal, hyperplastic and adenomatous parathyroid tissue was analysed at 2 and 4 days and 1, 2, 4, 7 and 12 weeks after transplantation to athymic mice. The transplants were examined by light and electron microscopy, immunohistochemistry and autoradiography. Vessels were detected by monoclonal antibodies specific for mouse and human endothelial cells. Immunohistochemistry demonstrated ingrowth of vessels from the host into the transplant and at one week numerous capillary sprouts were observed in the peripheral parts of the transplants. During the first week, peak levels of proliferation (labelling index) were observed in endothelial cells and capsular fibroblasts, and the proliferative capacity of endothelial cells was most pronounced in adenoma transplants. Fenestrated capillaries were observed in hyperplastic and adenomatous transplants, but not in transplants of normal tissue. In conclusion, revascularisation of transplanted human parathyroid tissue is enabled by ingrowth of vessels from the host into the transplant. The proliferative capacity of endothelial cells is higher and the process of maturation is faster in hyperplastic and adenomatous tissue compared to normal tissue.

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

“…Fresh human PT tissue has proven functional when transplanted subcutaneously into athymic 238 mice (3,4). We have in these previous studies found a high take ratio, preserved morphology and a high area fraction of viable xenotransplanted normal, hyperplastic and adenomatous PT tissue, and we have further observed that adenomatous PT tissue had the highest proliferation rate and that transplanted PT tissue secretes human PTH (3).…”

“…It was, however, also found that the transplants showed varying degrees of cell disintegration (3). Capillary sprouting into the periphery of the transplants was observed during the first week, but only at 4 to 7 weeks were mature capillaries noticed (4). Despite this, measurable amounts of PTH from the transplants were observed at one week after transplantation.…”

“…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).…”

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

“…These findings indicate that it is even mandatory to simultaneously assay angiogenesis and endocrine function to really address transplant-induced, and thus specific, angiogenic activity. Ander et al (8) studied in detail early angiogenesis of human parathyroid tissue transplanted into nude mice. With species-specific antibodies, mouse-human microvessel chimeras were histologically detectable in the first week.…”

“…Likewise, parathyroid tissue can induce angiogenesis in vitro (6) and in vivo (7). Angiogenic activity was observed during the first week after transplantation (8). Moreover, it was shown that transplanted parathyroid tissue is capable of spontaneous reinnervation along newly built blood vessels after 1 week (9).…”