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

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 journal › Article › Academic › peer-review

37 Citations (Scopus)

178 Downloads (Pure)

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 language	English
Pages (from-to)	913-925
Number of pages	13
Journal	Stem Cell Reports
Volume	16
Issue number	4
Early online date	27-Feb-2021
DOIs	https://doi.org/10.1016/j.stemcr.2021.02.011
Publication status	Published - 13-Apr-2021

Keywords

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

Access to Document

10.1016/j.stemcr.2021.02.011Licence: CC BY

Generation and Differentiation of Adult Tissue-Derived Human Thyroid OrganoidsFinal publisher's version, 3.58 MBLicence: CC BY

Handle.net

Persistent link

Cite this

@article{f23d3021e34c4561b1c6f8b15b49b903,

title = "Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids",

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.",

keywords = "EMBRYONIC STEM-CELLS, HORMONE REPLACEMENT, LONG-TERM, IN-VITRO, MOUSE, EXPRESSION, EXPANSION, STIMULATION, SYSTEM, GENES",

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

year = "2021",

month = apr,

day = "13",

doi = "10.1016/j.stemcr.2021.02.011",

language = "English",

volume = "16",

pages = "913--925",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Cell Press",

number = "4",

}

TY - JOUR

T1 - Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids

AU - Ogundipe, Vivian M L

AU - Groen, Andries H

AU - Hosper, Nynke

AU - Nagle, Peter W K

AU - Hess, Julia

AU - Faber, Hette

AU - Jellema, Anne L

AU - Baanstra, Mirjam

AU - Links, Thera P

AU - Unger, Kristian

AU - Plukker, John T M

AU - Coppes, Rob P

PY - 2021/4/13

Y1 - 2021/4/13

N2 - 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.

AB - 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.

KW - EMBRYONIC STEM-CELLS

KW - HORMONE REPLACEMENT

KW - LONG-TERM

KW - IN-VITRO

KW - MOUSE

KW - EXPRESSION

KW - EXPANSION

KW - STIMULATION

KW - SYSTEM

KW - GENES

U2 - 10.1016/j.stemcr.2021.02.011

DO - 10.1016/j.stemcr.2021.02.011

M3 - Article

C2 - 33711265

SN - 2213-6711

VL - 16

SP - 913

EP - 925

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 4

ER -

Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids

Abstract

Keywords

Access to Document

Handle.net

Fingerprint

Cite this