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

Abstract

The thyroid gland captures 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 and 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, functional human thyroid organoids could pave the way to explore new therapeutic approaches. Here we report the generation of transplantable thyroid organoids derived from human embryonic stem cells capable of restoring plasma thyroid hormone in athyreotic mice as a proof of concept for future therapeutic development.

Thyroid‐on‐a‐Chip: An Organoid Platform for In Vitro Assessment of Endocrine Disruption

“…The thyroid organoid culture tended to develop with significant variability in size, cell types, and functional capacity within the gel matrix drop. [ 22 ] In an effort to reduce organoid heterogeneity, fully differentiated thyroid follicles were retrieved from the gel matrix by enzymatic digestion. Subsequently, we collected structures from 30 to 100 µm in size through filtration.…”

“…[50] To overcome these limitations, few ESC-derived organoid models have successful been differentiated, which showed exceptional recapitulation of in vivo-like T4 secretion. [22] Recently, the incorporation of organoids in OoC systems has been suggested to create superior organoid models with controllable physical and biochemical properties. [13,25] Some advantages of using microfluidic systems include mimicking physiological blood flow, precise control over organoids size and number, and improvement of organoid functionality upon hydrodynamic, mechanical, or electrical stimuli.…”

“…[ 17–21 ] However, a recent model based on the overexpression of NKX2‐1 and PAX8 genes in hESCs demonstrated the fully generation of functional organoids in vitro, which showed regenerative capabilities when transplanted in thyroid‐ablated mice. [ 22 ] Recently, functional thyroid organoids were successfully derived from murine and human adult tissues. [ 23,24 ]…”

“…[17][18][19][20][21] However, a recent model based on the overexpression of NKX2-1 and PAX8 genes in hESCs demonstrated the fully generation of functional organoids in vitro, which showed regenerative capabilities when transplanted in thyroid-ablated mice. [22] Recently, functional thyroid organoids were successfully derived from murine and human adult tissues. [23,24] The incorporation of organoids into organ-on-a-chip (OoC) devices, also known as microphysiological systems, has been proposed as a promising synergistic strategy to capitalize the full potential of organoids for drug screening.…”

Type 1 Diabetes Mellitus: A Review on Advances and Challenges in Creating Insulin Producing Devices

“…They self-renew and self-organize into complex organ-like tissues, providing an outstanding potential to model human organ development [ 85 , 86 ]. Their potential is great and, for instance, just recently Romiti et al successfully developed a transplantable human thyroid organoid from hESC [ 87 ].…”