US EPA

9298412 

Journal Article 

Preservation of functioning human thyroid organoids in the scid mouse: 1. System characterization 

Martin, A; Valentine, M; Unger, P; Lichtenstein, C; Schwartz, AE; Friedman, EW; Shultz, LD; Davies, TF; , 

1993 

Yes 

Journal of Clinical Endocrinology and Metabolism
ISSN: 0021-972X
EISSN: 1945-7197 

ENDOCRINE SOC 

WASHINGTON 

305-310 

English 

8345031 

WOS:A1993LR71900003 

We have characterized a system for preserving reconstituted human thyroid 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 normal 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 examination of human thyroid organoids demonstrated widespread neofollicle formation and colloid accumulation which stained positive for human thyroglobulin (hTg). Although there were no changes in murine serum T4 levels; the transplanted thyroid epithelial cells secreted hTg into the scid mouse circulation (with an average level of 29 micrograms/L). In addition, hTg release was stimulated in vivo by ip administration of recombinant human TSH (0.1-1.0 IU/mouse) achieving greater than 20-fold increases in scid mouse serum hTg levels. In situ immunohistochemistry showed that thyroid organoids derived from patients with Graves' disease retained scattered lymphocytes in peripolesis with the thyroid epithelial cells; those lymphocytes were identified as human T cells of the memory (CD45RO +), rather than naive, type. These data demonstrate that functioning human thyroid organoids establish in scid mice and remain responsive to TSH stimulation. The system offers a unique opportunity to examine human thyroid-lymphocyte interaction within the confines of a predictable animal model.