Stem cell-derived organoids mimic human parathyroid tissue

A study published Oct.
27 in the journal Stem Cell Reports suggests that patient-derived parathyroid organoids (PTOs) may pave the way
for future physiological studies and drug screening applications.

Senior researcher Schelto Kruijff at the University Medical Center Groningen said: "We are the first group in the world to be able to isolate parathyroid stem cells and keep these cells as organoids in our laboratory for a long time
.
Our study uses PTO as a new model
for parathyroid disease research.
”

Parathyroid disease is characterized by altered excretion of parathyroid hormone, resulting in abnormal serum calcium concentrations
.
The development of parathyroid-targeted therapies and imaging tracers can benefit
from in vitro models.
Organoids are developed from stem cells that closely summarize the three-dimensional structure of tissue structure
and cell composition.
These models have proven to be very useful for studying tumor behavior and assessing drug response, and provide a platform
for long-term in vitro experiments.

"We have shown that the parathyroid glands contain stem cells
capable of producing organoids.
These organoids mimic a patient's condition, are able to produce hormones, express specific markers, and show similar responses to drugs," Kruijff said
.

In this study, Kruijff and Rob Coppes from the University Medical Center of Groningen set out to build a patient-derived PTO model
that represents human parathyroid tissue.
The researchers obtained benign hyperplastic parathyroid tissue
from patients who underwent parathyroid surgery.
They isolated parathyroid stem cells from tissues and examined their potential to
expand and form PTOs.

PTOs are similar
to the original tissue in terms of gene and protein expression levels and functions.
Other results showed that increases and decreases in hormone secretion were associated
with changes in calcium concentration and parathyroid hormone-lowering drugs.
In addition, the researchers found specific uptake
of parathyroid-targeting tracers in PTOs.
Overall, the results suggest that these organoids can mimic human parathyroid function
.

One limitation of the study is the lack of the original microenvironment, including blood vessels and fluctuating concentrations
of extracellular signals.
However, functional tests and tracer experiments have shown that PTOs are a well-suited model, similar to functional parathyroid tissue
.

In future studies, the researchers plan to transplant these organoids into rats with hypoparathyroidism to study their function in
a living animal model.
"These organoids could be used to test future parathyroid-targeting drugs and imaging tracers
.
" When organoids are used, less animal testing is required," Kruijff said
.
"In addition, this technology can be used to grow healthy parathyroid organoids to treat patients with
hypoparathyroidism.
"

Milou E.
Noltes, Luc H.
J.
Sondorp, Laura Kracht, Inê s F.
Antunes, René Wardenaar, Wendy Kelder, Annelies Kemper, Wiktor Szymanski, Wouter T.
Zandee, Liesbeth Jansen, Adrienne H.
Brouwers, Robert P.
Coppes, Schelto Kruijff.
Patient-derived parathyroid organoids as a tracer and drug-screening application model.
Stem Cell Reports, 2022