A new animal model to assess angiogenesis and endocrine function of parathyroid heterografts in vivo.
BACKGROUND
It is still a matter of investigation how angiogenesis and restoration of gland 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 mice (CD1-nu; 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, intact human parathyroid hormone levels were detectable by species-specific enzyme-linked immunosorbent assay analysis of plasma samples on day 5 after transplantation and increased by 2.5-fold over the observation period (19 days) in contrast with controls. Plasma Ca levels revealed no differences between the groups. On day 5 after transplantation, intravital fluorescence microscopy revealed murine angiogenic microvessels sprouting along nonperfused human donor vessels, and 1 week later functional microvasculature was established in all parathyroid transplants. Histologic analysis revealed well-vascularized endocrine tissue. In contrast, control grafts were necrotic and partly resorbed; they exhibited no angiogenic activity or well-vascularized fat cells indicating fatty degeneration. In addition, species-specific Western blot analysis revealed vascular endothelial growth factor expression of parathyroid transplants rather than functional vessel density as the functional parameter of angiogenesis determining transplant function in vivo.


CONCLUSIONS
This model may serve to understand mechanisms associated with specific parathyroid transplant angiogenesis and its significance for transplant function to optimize clinical success of autotransplantation in therapy-resistant patients.
Strieth
Sebastian
S
Institute for Surgical Research, Klinikum Grosshadern, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany. sebastian.strieth@med.uni-muenchen.de
von Johnston
Verena
V
Eichhorn
Martin E
ME
Eichhon
Martin E
ME
Enders
Georg
G
Krasnici
Senat
S
Thein
Eckart
E
Hammer
Claus
C
Dellian
Marc
M
D000818:Animals; D002118:Calcium / Q000097:blood; D006801:Humans; D008297:Male; D051379:Mice; D023421:Models, Animal; D018919:Neovascularization, Physiologic; D010280:Parathyroid Glands / Q000098:blood supply / Q000473:pathology / Q000637:transplantation*; D010281:Parathyroid Hormone / Q000097:blood*; D014183:Transplantation, Heterologous
D010281:Parathyroid Hormone; D002118:Calcium