Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids

Vivian M L Ogundipe, Andries H Groen, Nynke Hosper, Peter W K Nagle, Julia Hess, Hette Faber, Anne L Jellema, Mirjam Baanstra, Thera P Links, Kristian Unger, John T M Plukker, Rob P Coppes*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Total thyroidectomy as part of thyroid cancer treatment results in hypothyroidism requiring lifelong daily thyroid hormone replacement. Unbalanced hormone levels result in persistent complaints such as fatigue, constipation, and weight increase. Therefore, we aimed to investigate a patient-derived thyroid organoid model with the potential to regenerate the thyroid gland. Murine and human thyroidderived cells were cultured as organoids capable of self-renewal and which expressed proliferation and putative stem cell and thyroid characteristics, without a change in the expression of thyroid tumor-related genes. These organoids formed thyroid-tissue-resembling structures in culture. (Xeno-)transplantation of 600,000 dispersed organoid cells underneath the kidney capsule of a hypothyroid mouse model resulted in the generation of hormone-producing thyroid-resembling follicles. This study provides evidence that thyroid-lineagespecific cells can form organoids that are able to self-renew and differentiate into functional thyroid tissue. Subsequent (xeno-)transplantation of these thyroid organoids demonstrates a proof of principle for functional miniature gland formation.

Original languageEnglish
Pages (from-to)913-925
Number of pages13
JournalStem Cell Reports
Volume16
Issue number4
Early online date27-Feb-2021
DOIs
Publication statusPublished - 13-Apr-2021

Keywords

  • EMBRYONIC STEM-CELLS
  • HORMONE REPLACEMENT
  • LONG-TERM
  • IN-VITRO
  • MOUSE
  • EXPRESSION
  • EXPANSION
  • STIMULATION
  • SYSTEM
  • GENES

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