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

Area of Science:

• Endocrinology
• Immunology
• Regenerative Medicine

Background:

• Human thyroid follicles are crucial for hormone production.
• Studying thyroid function and diseases often requires suitable in vivo models.
• Current models may not fully replicate human thyroid physiology or immune interactions.

Purpose of the Study:

• To establish a functional human thyroid organoid system in vivo.
• To assess the viability and function of transplanted human thyrocytes in immunodeficient mice.
• To investigate human thyroid-lymphocyte interactions in a xenograft model.

Main Methods:

• Construction of human thyroid organoids from normal and abnormal thyroid cells.
• Subcutaneous transplantation of organoids into severe combined immunodeficiency (scid) mice.
• Histological examination, immunohistochemistry, and serum analysis (hTg, T4) post-transplantation.
• In vivo stimulation with recombinant human thyroid-stimulating hormone (TSH).

Main Results:

• Successful establishment of human thyroid organoids in scid mice, showing neofollicle formation and colloid accumulation.
• Transplanted cells secreted human thyroglobulin (hTg) into mouse circulation, responsive to TSH stimulation.
• Graves' disease organoids exhibited interactions with human memory T cells, suggesting immune involvement.

Conclusions:

• Functioning human thyroid organoids can be established and maintained in scid mice.
• The model supports TSH-dependent thyroid function and allows for in vivo study of thyroid-immune cell interactions.
• This system provides a valuable platform for investigating human thyroid diseases and potential therapies.