Human adrenocortical cell xenotransplantation: Model of cotransplantation of human adrenocortical cells and 3T3 cells in scid mice to form vascularized functional tissue and prevent adrenal insufficiency

To establish an experimental model for replacement of endocrine organ function by xenotransplantation, human adrenocortical cells from postnatal donors were transplanted beneath the kidney capsule of adrenalectomized scid mice together with mitomycin C-treated 3T3 cells that secrete FGF. Adrenocortical cells from seven donors, male and female, ranging from 6-50 years of age, were used. 12 of 13 animals survived > 16 days following surgery. After 50 days they were sacrified to allow assessment of the histology and ultrastructure of tissue formed from the transplanted cells. Only 1 of 23 adrenalectomized sham-operated animals survived > 16 days. In all surviving animals, vascularized adrenocortical tissue formed at the site of transplantation. Cortisol, the normal human glucocorticoid, was present in the plasma of these animals, replacing corticosterone, the mouse glucocorticoid. Some animals, but not most, had measurable aldosterone. The tissue formed from the transplanted cells showed histological and ultrastructural features of normal adrenal cortex. Mitochondria had tubulo-vesicular cristae and there were prominent microvilli between cells. Tissues had a well-developed vasculature, sometimes with large sinusoidal vessels. Proliferation in the transplant tissues was very low. These results show that tissue formed from transplanted human adrenocortical cells is able to replace the essential functions of the adrenal gland in scid mice. This demonstrates that transplanted human endocrine cells can functionally replace a surgically removed endocrine organ in a host animal.