Functional model of rat thyroid follicles cultured in Matrigel

Хоруженко, А. И.; Miot, Françoise; Massart, C.; Sande, Jacqueline Van; Dumont, Jacques Emile; Beauwens, Renaud; Boom, Alain

doi:10.1530/ec-21-0169

Cited by 7 publications

(6 citation statements)

References 25 publications

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“…The successfully established rat thyroid follicle culture remained viable and maintained a follicular architecture with correct cellular polarity for at least 14 days. Expression of characteristic basolateral and apical specific proteins, including ZO-1, ezrin, pendrin, MCT8, and thyroglobulin, evinced correct follicular polarization, similar to previous reports (Delmarcelle et al, 2014;Deisenroth et al, 2020;Khoruzhenko et al, 2021). Moreover, these rat follicle cultures restored their capability to synthesize and secrete THs, predominantly T4, in the presence of TSH.…”

Section: Discussionsupporting

confidence: 88%

“…from rat and porcine tissues. Again, the structural and functional integrity was maintained by embedding follicles in collagen or Matrigel (Denef et al, 1980;Gärtner et al, 1985;Khoruzhenko et al, 2021). However, to the best of our knowledge, no rat 3D thyroid in vitro model has previously been published, in which chemical-induced perturbation of TH release could be demonstrated.…”

Section: Discussionmentioning

confidence: 99%

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A rodent thyroid-liver chip to capture thyroid toxicity on organ functional level

Karwelat

Kühnlenz

Steger‐Hartmann

et al. 2022

ALTEX

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Endocrine disruption by environmental chemicals continues to be a concern for human safety. The rat, a widely used model organism in toxicology, is very sensitive to chemical-induced thyroid perturbation, e.g. histopathological alterations in thyroid tissue. Species differences in the susceptibility to thyroid perturbation lead to uncertainty in human safety risk assessments. Hazard identification and characterization of chemically induced thyroid perturbation would therefore benefit from in vitro models addressing different mechanisms of action in a single functional assay, ideally across species. We here introduce a rat thyroid-liver chip that enables simultaneous identification of direct and indirect (liver-mediated) thyroid perturbation on organ-level functions in vitro. A second manuscript describes our work toward a human thyroid-liver chip (Kühnlenz et al., 2022). The presented microfluidic model consisting of primary rat thyroid follicles and liver 3D spheroids maintain a tissue-specific phenotype for up to 21 days. More precisely, the thyroid model exhibits a follicular architecture expressing basolateral and apical markers and secretes T4. Likewise, liver spheroids retain hepatocellular characteristics, e.g. a stable release of albumin and urea, the presence of bile canalicular networks, and the formation of T4-glucuronide. Experiments with reference chemicals demonstrated proficiency to detect direct and indirect mechanisms of thyroid perturbation through decreased thyroid hormone secretion and increased gT4 formation, respectively. Prospectively this rat thyroid-liver chip model, together with its human counterpart, may support a species-specific quantitative in vitro to in vivo extrapolation to improve a data-driven and evidence-based human safety risk assessment with significant contributions to the 3R principles. *

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

A rodent thyroid-liver chip to capture thyroid toxicity on organ functional level

Karwelat

Kühnlenz

Steger‐Hartmann

et al. 2022

ALTEX

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“…The generation of organoids with high efficiency is essential to explore mechanisms related to developmental biology, disease progression and therapies. Thyroid organoids have been generated from the fetal and adult thyroid tissue of rats and humans 23–25,66,67 . Those protocols result in three-dimensionally organized pure population of follicular structures with high degree of differentiation, iodine uptake capability which results in functional activity.…”

Section: Discussionmentioning

confidence: 99%

“…Thyroid organoids have been generated from the fetal and adult thyroid tissue of rats and humans [23][24][25]66,67 . Those protocols result in three-dimensionally organized pure population of follicular structures with high degree of differentiation, iodine uptake capability which results in functional activity.…”

Section: The Generation Of Organoids With High E Ff I C I E N C Y I S...mentioning

confidence: 99%

Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism

Romitti¹,

Fonseca²,

Doumont³

et al. 2021

Preprint

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The function of the thyroid gland is to capture iodide in order to synthesize hormones that act on almost all tissues and are essential for normal growth and metabolism. Low plasma levels of thyroid hormones lead to hypothyroidism, which is one of the most common disorder in humans which is not always satisfactorily treated by lifelong hormone replacement. Therefore, in addition to the lack of in vitro tractable models to study human thyroid development, differentiation and maturation, there is a need for new therapeutic approaches that involve replacement of thyroid tissue responsive to changing demands for thyroid hormone. Here we report the first transplantable thyroid organoids derived from human embryonic stem cells capable of restoring plasma thyroid hormone to athyreotic mice as a proof of concept for future therapeutic development.

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“…For example, some researchers have recently demonstrated the ability of a microfluidic device to maintain human Graves’ disease tissue enabling the isolation of Graves’ disease-specific EVs [ 87 ]. Others described a method of 3D rat thyroid follicles culture in Matrigel that reproduces physiological follicle structure and activity [ 88 ]. Finally, advances in generating thyroid organoids could also help and be inspiring for thyroid-derived EV functional studies [ 89 , 90 ].…”

Section: Concerns and Further Directionsmentioning

confidence: 99%

Role of Extracellular Vesicles in Thyroid Physiology and Diseases: Implications for Diagnosis and Treatment

2022

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Extracellular vesicles are spherical subcellular structures delimited by a lipid bilayer and released by most cells in the human body. They are loaded with a myriad of molecules (i.e., nucleic acids and proteins) depending on their cell of origin and provide the ability to transmit a message to surrounding or distant target cells. In several organs, including the thyroid, abundant recent literature reports that extracellular vesicles are responsible for intercellular communication in physiological and pathological processes, and that their utilization as a potential biomarker of pathological states (i.e., cancer, autoimmune diseases) or as therapeutic delivery vehicles promise clinical options. In this review, we present the current knowledge and understanding regarding the role of extracellular vesicles in developing thyroid diseases and diagnosis.

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Functional model of rat thyroid follicles cultured in Matrigel

Cited by 7 publications

References 25 publications

A rodent thyroid-liver chip to capture thyroid toxicity on organ functional level

A rodent thyroid-liver chip to capture thyroid toxicity on organ functional level

Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism

Role of Extracellular Vesicles in Thyroid Physiology and Diseases: Implications for Diagnosis and Treatment

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