March 03, 2005

Ein neues Tiermodell zur Analyse von Angiogenese und endokriner Funktion bei Transplantation von humanem Nebenschilddrüsengewebe auf die athyme Nacktmaus in vivo

It is unclear how angiogenesis and restoration of perfusion determine graft function after free parathyroid autotransplantation.We provide a new animal model allowing simultaneous and repetitive in vivo assessment of angiogenesis and endocrine function of parathyroid transplants. Methods:Fresh human parathyroid tissue from patients with secondary hyperparathyroidism was grafted into dorsal skinfold chamber preparations of athymic nude mi(CD1-nu BR; n=8). Equivalent pieces of the same human donor specimens were heat-inactivated and served as control grafts (n=7).Results:In all animals receiving parathyroid transplants human parathyroid hormone levels were detectable by species-specific ELISA analysis of plasma samples on day 5 after transplantationand increased by 2.5 fold over the observation (19 days) in contrst to controls (day 19: 82.5+/-29.3 vs. 0.0+/-0.0 pg/ml; p<0.05).Plasma Calcium-levels revealed no differences between the groups. On day 5 after transplantation intravital fluorescence microscopy revealed first murine angiogenic microvessels sprouting alongg non-perfused human donor vessels and one week later functional microvasculature was established in all parathyroid transplants. Histological analysis of HE- and vWF- contrast, control grafts were either necrotic and partly resorbed exhibiting no angiogenic activity or revealed well vascularized fat cells indicating fatty degeneration. Aditionally, species-specific Western blot analysis revealed vascular endothelial growth factor expression of parathyroid transplants as functional parameter of angiogenesis determining transplant function in vivo. Conclusion: This model may serve to understand mechanisms associated with specific parathyroid transplant angiogenesis and its significance for transplant function in order to optimize clinical success of autotransplantation in therapy-resistant patients.

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