PRESERVATION OF FUNCTIONING HUMAN THYROID ORGANOIDS IN THE SCID MOUSE.1. SYSTEM CHARACTERIZATION

We have characterized a system for preserving reconstituted human thyr oid follicles in vivo by transplanting human thyrocytes into mice with severe combined immunodeficiency (scid mice). Human thyroid organoids were constructed from thyroid monolayer cells derived from both norma l and abnormal thyroid tissue, and embedded within a basement membrane preparation which was then transferred sc to scid mice. As early as 4 weeks, and as late as 3 months post transplantation, histological exa mination of human thyroid organoids demonstrated widespread neofollicl e formation and colloid accumulation which stained positive for human thyroglobulin (hTg). Although there were no changes in murine serum T4 levels, the transplanted thyloid epithelial cells secreted hTg into t he scid mouse circulation (with an average level of 29 mug/L). In addi tion, hTg release was stimulated in vivo by ip administration of recom binant human TSH (0.1-1.0 IU/mouse) achieving greater than 20-fold inc reases in scid mouse serum hTg levels. In situ immunohistochemistry sh owed that thyroid organoids derived from patients with Graves' disease retained scattered lymphocytes in peripolesis with the thyroid epithe lial cells; those lymphocytes were identified as human T cells of the memory (CD45RO +), rather than naive, type. These data demonstrate tha t functioning human thyroid organoids establish in scid mice and remai n responsive to TSH stimulation. The system offers a unique opportunit y to examine human thyroid-lymphocyte interaction within the confines of a predictable animal model.