Article
Simultaneous in vivo analysis of angiogenesis and endocrine function after parathyroid heterotransplantation
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Published: | September 22, 2005 |
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It is still a matter of investigation how angiogenesis and restoration of gland perfusion determine graft function after free parathyroid autotransplantation. We here provide a new animal model allowing simultaneous and repetitive in vivo assessment of angiogenesis and endocrine function of parathyroid transplants.
Fresh human parathyroid tissue from patients with secondary hyperparathyroidism was grafted into dorsal skinfold chamber preparations of athymic nude mice (CD1-nu; n=8). Equivalent pieces of the same human donor specimens were heat-inactivated and served as control grafts (n=7).
In all animals receiving parathyroid transplants intact human parathyroid hormone levels were detectable by species-specific ELISA analysis of plasma samples on day 5 after transplantation and increased by 2.5 fold over the observation period (19 days) in contrast to controls. Plasma Ca2+ levels revealed no differences between the groups.
On day 5 after transplantation intravital fluorescence microscopy revealed first murine angiogenic microvessels sprouting along non-perfused human donor vessels and one week later functional microvasculature was established in all parathyroid transplants. Histological analysis revealed well vascularized endocrine tissue. In contrast, control grafts were either necrotic and partly resorbed exhibiting no angiogenic activity or revealed well vascularized fat cells indicating fatty degeneration. Additionally, species-specific Western blot analysis revealed vascular endothelial growth factor expression of parathyroid transplants rather than functional vessel density as functional parameter of angiogenesis determining transplant function in vivo.
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.