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

doi:10.1016/j.stemcr.2021.02.011

Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids

Stem Cell Reports. 2021 Apr 13;16(4):913-925. doi: 10.1016/j.stemcr.2021.02.011. Epub 2021 Mar 11.

Authors

Affiliations

¹ Department of Biomedical Sciences of Cells and Systems, Section of Molecular Cell Biology, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands; Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands.
² Department of Biomedical Sciences of Cells and Systems, Section of Molecular Cell Biology, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands; Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands.
³ Department of Biomedical Sciences of Cells and Systems, Section of Molecular Cell Biology, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands; Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands; Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands.
⁴ Research Unit Radiation Cytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg 85764, Germany; Department of Radiation Oncology, University Hospital, LMU Munich, Munich 81377, Germany.
⁵ Department of Biomedical Sciences of Cells and Systems, Section of Molecular Cell Biology, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands.
⁶ Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands.
⁷ Department of Surgical Oncology, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands.
⁸ Department of Biomedical Sciences of Cells and Systems, Section of Molecular Cell Biology, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands; Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen 9713 GZ, the Netherlands. Electronic address: r.p.coppes@umcg.nl.

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 thyroid-derived 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-lineage-specific 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.

Keywords: hypothyroidism; regeneration; stem cells; thyroglobulin; thyroid cancer; thyroid-tissue-derived organoids; xeno-transplanation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Biomarkers, Tumor / metabolism
Cell Differentiation*
Cell Self Renewal
Disease Models, Animal
Humans
Hypothyroidism / pathology
Mice
Organoids / cytology*
Stem Cells / cytology
Thyroid Gland / cytology*
Tissue Culture Techniques

Substances

Biomarkers, Tumor